Oral care method and kit

ABSTRACT

A method of moisturizing while decolonizing mammalian tissue, the method comprising applying a multi-valent cationic antiseptic composition to the tissue, and applying a moisturizer composition to at least a portion of the same tissue; wherein the mammalian tissue is oral tissue of a subject; wherein the multi-valent cationic antiseptic is other than a metal ion; and wherein the applied compositions essentially exclude any component which causes a precipitate when combined with a multi-valent cationic antiseptic contained in the multi-valent cationic antiseptic composition when tested according to Test Method F, and/or wherein the moisturizer composition is such that a log reduction in the number of viable bacterial cells of at least 2 is provided when 10 6  cfu of  Pseudomonas aeruginosa  are combined with a mixture 1.1 g of the moisturizer composition and 1.5 g of the multi-valent cationic antiseptic composition containing 0.12 weight percent of the multi-valent cationic antiseptic according to Test Method B; an oral care kit comprising a composition comprising the multi-valent cationic antiseptic and the moisturizer composition; and a method of moisturizing oral tissue of a patient requiring intubation using the moisturizer composition and an endotracheal tube coated or impregnated with a cationic antiseptic are provided.

This application claims the benefit of U.S. Provisional Application No.61/176,788, filed May 8, 2009, which is incorporated herein by referencein its entirety.

BACKGROUND

Nosocomial pneumonias are a common hospital-acquired infection. The riskof such infections is believed to increase dramatically, for example,six to twenty fold, when mechanical ventilation is used on a patient.Ventilator associated pneumonia (VAP) is associated with highattributable mortality, which has been reported to be in the range of 33to 50 percent. Published studies and Meta-Analysis have shown that oralcare of mechanically ventilated patients with a chlorhexidine gluconate(CHG) containing mouth rinse significantly help reduce the incidence ofVAP. Studies have also shown that dental plaque in ventilated patientsbecomes populated with pathogens which can then be aspirated, so removaland treatment of dental plaque is critical in the prevention of VAP.Ventilated patients as well as a significant segment of the populationalso suffer from xerostomia (dry mouth). Without the normal salivaryflow, which not only mechanically washes off bacteria but also containsenzymes, antibodies, and other components important to the immunesystem, xerostomia favors bacterial proliferation. In the case ofmechanically ventilated patients, the xerostomia has been treated byperiodic application of a mouth moisturizer, while the CHG treatmentmentioned above is intended to help reduce or prevent dental plaque,gingivitis, periodontal disease, as well as overgrowth of opportunisticmicroorganisms. In some instances, the mouth moisturizers dry out andbecome white or peelable upon drying. This is an undesirablecharacteristic, not only because health care workers have great concernabout the general appearance of their patients, but it also decreasesthe efficacy of the moisturizer.

Certain oral hygiene products, for treating ventilated patients, arecommercially available. Such products pre-package certain formulationsand applicators, for example, mouth washes or rinses, oral debridingagents, mucosal moisturizers, swabs, and brushes.

However, there continues to be a need for improved methods and productswhich provide greater flexibility and efficacy in treating patientsaccording to their individual indications.

SUMMARY OF THE INVENTION

The present invention provides a method of moisturizing whiledecolonizing mammalian oral tissue as well as an oral care kit andarticles used therein for treating oral tissue. It has now been found,that oral tissue moisturizers presently used in commercial kits with aCHG oral rinse significantly reduce the antibacterial activity of theCHG oral rinse, and that components of these kits chemically inactivatethe CHG. It is extremely important that any treatment regiment formechanically ventilated patients address both the reduction ofmicroorganisms (plaque removal and reduction of opportunistic organismsin the oral cavity) and xerostomia without having the products used foraddressing these problems interact with each other to reduce theeffectiveness of any one of the products when used in combination.

It has now also been found that certain oral tissue moisturizers can beselected, which when used with a CHG oral rinse do not reduce theantibacterial activity of the CHG rinse or reduce the antibacterialactivity of the CHG rinse to a much lesser extent than oral tissuemoisturizers presently used with a CHG oral rinse. We have further foundthat effective moisturizers can be formulated that can form softflexible coatings that do not form self supporting films that may turnopaque and/or peel off. This applies as well to CHG oral gels and otherCHG oral preparations.

Accordingly, in one embodiment, there is provided a method ofmoisturizing while decolonizing mammalian tissue, the method comprising:

applying a multi-valent cationic antiseptic composition to oral tissue,and

applying a moisturizer composition to at least a portion of the oraltissue;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with a multi-valent cationicantiseptic used in the multi-valent cationic antiseptic composition whentested according to Test Method F;

wherein the multi-valent cationic antiseptic is other than a metal ion.

In another embodiment, there is provided a method of moisturizing whiledecolonizing mammalian tissue, the method comprising:

applying a multi-valent cationic antiseptic to the tissue, and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein the substantive moisturizer composition is such that a logreduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853) arecombined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent (0.00134 M) of the multi-valent cationicantiseptic according to Test Method B.

In another embodiment, there is provided an oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a moisturizer composition;

wherein each composition is for application to oral tissue of a subject;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the multi-valent cationicantiseptic when tested according to Test Method F;

wherein the multi-valent cationic antiseptic is other than a metal ion.

In another embodiment, there is provided an oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein the substantive moisturizer composition is such that a logreduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853) arecombined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of the multi-valent cationic antisepticcomposition containing 0.12 weight percent of the multi-valent cationicantiseptic according to Test Method B.

For certain embodiments, including the above embodiments, thesubstantive moisturizer composition is such that a log reduction in thenumber of viable bacterial cells of at least 3 is provided. For certainof these embodiments, preferably the log reduction in the number ofviable bacterial cells is at least 4, or even at least 5.

In another embodiment, there is provided a method of moisturizing whiledecolonizing mammalian tissue, the method comprising:

applying a multi-valent cationic antiseptic composition to the tissue,and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that the multi-valent cationicantiseptic composition combined with the substantive moisturizercomposition achieves a log reduction in the number of viable bacterialcells of at least 2 when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853)are combined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B. For certain of these embodiments, theanionic compound is selected from the group consisting of polyanions ofpolycarboxylates, polysulfonates, polysulfates, and polyphosphates;chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,alkylsulfonates, arylsulfonates, alkylcarboxylates, arylcarboxylates,alkylphosphates, arylphosphates; and combinations thereof; wherein thealkyl groups have a chain length of greater than four carbon atoms, andthe aryl groups include at least 6 carbon atoms.

In another embodiment, there is provided a method of moisturizing whiledecolonizing mammalian tissue, the method comprising:

applying a multi-valent cationic antiseptic composition to the tissue,and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that greater than 40 percent ofthe multivalent cationic antiseptic, which was soluble in themulti-valent cationic antiseptic composition, remains soluble when themulti-valent cationic antiseptic composition and the substantivemoisturizer composition are combined. For certain of these embodiments,the anionic compound is selected from the group consisting of polyanionsof polycarboxylates, polysulfonates, polysulfates, and polyphosphates;chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,alkylsulfonates, arylsulfonates, alkylcarboxylates, arylcarboxylates,alkylphosphates, arylphosphates; and combinations thereof; wherein thealkyl groups have a chain length of greater than four carbon atoms, andthe aryl groups include at least 6 carbon atoms.

In another embodiment, there is provided an oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that the multi-valent cationicantiseptic composition combined with the substantive moisturizercomposition achieves a log reduction in the number of viable bacterialcells of at least 2 when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853)are combined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B. For certain of these embodiments, theanionic compound is selected from the group consisting of polyanions ofpolycarboxylates, polysulfonates, polysulfates, and polyphosphates;chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,alkylsulfonates, arylsulfonates, alkylcarboxylates, arylcarboxylates,alkylphosphates, arylphosphates; and combinations thereof; wherein thealkyl groups have a chain length of greater than four carbon atoms, andthe aryl groups include at least 6 carbon atoms.

In another embodiment, there is provided an oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that greater than 40 percent ofthe multivalent cationic antiseptic which was soluble in themulti-valent cationic antiseptic composition remains soluble when themulti-valent cationic antiseptic composition and the substantivemoisturizer composition are combined. For certain of these embodiments,the anionic compound is selected from the group consisting of polyanionsof polycarboxylates, polysulfonates, polysulfates, and polyphosphates;chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,alkylsulfonates, arylsulfonates, alkylcarboxylates, arylcarboxylates,alkylphosphates, arylphosphates; and combinations thereof; wherein thealkyl groups have a chain length of greater than four carbon atoms, andthe aryl groups include at least 6 carbon atoms.

For certain embodiments, including any one of the above embodiments, thesubstantive moisturizer composition when dry does not form a selfsupporting film.

In another embodiment there is provided a method of moisturizing oraltissue of a patient requiring intubation, the method comprising:

applying a moisturizer composition to at least a portion of the oraltissue, an endotracheal tube, or both;

inserting an endotracheal tube through the patient's oral cavity andinto the patient's trachea;

wherein the endotracheal tube is coated or impregnated with a cationicantiseptic;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the cationic antisepticwhen tested according to Test Method F; and

wherein the cationic antiseptic is other than a metal ion.

DEFINITIONS

The following terms are used herein according to the followingdefinitions.

“Oral tissue” refers to oral mucosal tissue, teeth, whether natural orprosthetic, within the oral cavity, tongue, and lips. For certainembodiments, preferably oral tissue is oral mucosal tissue.

“Mucosal tissue,” “mucous membranes,” and “mucosal membranes” and areused interchangeably and refer to the surfaces of the oral (e.g., mouth)cavity, and other similar tissues. Examples include mucosal membranessuch as buccal and gingival mucosal membranes.

“Decolonizing” and “Decolonization” refer to a reduction in the numberof microorganisms (e.g., bacteria) present in or on tissue that do notnecessarily cause immediate clinical symptoms. Ordinarily fewermicroorganisms are present in “colonized tissue” than in “infectedtissue.” When the tissue is completely decolonized the microorganismshave been “eradicated”.

“Effective amount” means the amount of the one or more antisepticcomponents when in a composition, as a whole, provides antimicrobial(including, for example, antiviral, antibacterial, or antifungal)activity that when applied in an amount, at a frequency, and for aduration, reduces, prevents, or eliminates one or more species ofmicrobes such that an acceptable level of the microbe results.Typically, this is a level low enough not to cause clinical symptoms,and is desirably a non-detectable level. It should be understood that inthe compositions of the present invention, the concentrations or amountsof the components, when considered separately, may not kill to anacceptable level, or may not kill as broad a spectrum of undesiredmicroorganisms, or may not kill as fast; however, when used togethersuch components may provide an enhanced antimicrobial activity (ascompared to the same components used alone under the same conditions).Also, it should be understood that (unless otherwise specified) thelisted concentrations of the components are for “ready to use” or “asused” compositions. The compositions can be in a concentrated form. Thatis, certain embodiments of the compositions can be in the form ofconcentrates that would be diluted by the user with an appropriatevehicle.

“Hydrophilic” or “water-soluble” refers to a material that will dissolvein deionized water (or other aqueous solution as specified) at atemperature of 23° C. in an amount of at least 7% by weight, preferablyat least 10% by weight, more preferably at least 20% by weight, evenmore preferably at least 25% by weight, even more preferably at least30% by weight, and most preferably at least 40% by weight, based on thetotal weight of the hydrophilic material and the water. The component isconsidered dissolved if after thoroughly mixing the compound with waterat 60° C. for at least 4 hours and allowing this to cool to 23-25° C.for 24 hours, and mixing the composition thoroughly it appears uniformclear solution without visible cloudiness, phase separation, orprecipitate in a jar having a path length of 4 cm. Typically when placedin 1×1 cm cell, the samples exhibit greater than 70% transmissionmeasured in a suitable spectrophotometer at a wavelength of 655 nm.

“Hydrophobic” or “water-insoluble” refers to a material that will notsignificantly dissolve in deionized water at 23° C. “Not significantly”means that the solubility in water of the material is less than 5% byweight, preferably less than 1% by weight, more preferably less than0.5% by weight, and even more preferably less than 0.1% by weight, basedon the total weight of the hydrophobic material and the water.Solubility can be determined by thoroughly mixing the compound withwater at the appropriate concentration at 23° C. for at least 24 hours(or at elevated temperature if that is necessary to dissolve thecompound), allowing this to sit at 23-25° C. for 24 hours, and observingthe sample. In a glass jar with a 4 cm path length the sample shouldhave evidence of a second phase which can be liquid or solid and may beseparated on the top, bottom, or distributed throughout the sample. Forcrystalline compounds care must be taken to avoid producing asupersaturated solution. The components should be mixed and observed.Cloudiness or presence of a visible precipitate or separate phaseindicates that the solubility limit has been exceeded. Typically whenplaced in 1×1 cm cell the sample has less than 70% transmission measuredin a suitable spectrophotometer at a wavelength of 655 nm. Forsolubility determinations less than that which can be observed with thenaked eye, the solubility is determined using radiolabeled compounds asdescribed under “Conventional Solubility Estimations” in Solubility ofLong-Chain Fatty Acids in Phosphate Buffer at pH 7.4, Henrik Vorum, et.al., Biochimica et. Biophysica Acta. 1126 (1992) 135-142.

“Stable” means physically stable or chemically stable, which are bothdefined in greater detail below. Preferred compositions are bothchemically and physically stable.

“Microorganism” or “microbe” or refers to bacteria, yeast, mold, fungi,protozoa, mycoplasma, as well as viruses (including lipid enveloped RNAand DNA viruses).

“Treat” or “treatment” means to improve the condition of a subjectrelative to the affliction, typically in terms of clinical symptoms ofthe condition.

“Subject” and “patient” includes humans, sheep, horses, cattle, pigs,dogs, cats, rats, mice, or other mammal.

“Enhancer” means a component that enhances the effectiveness of theantiseptic component such that when the composition less the antisepticcomponent and the composition less the enhancer component are usedseparately, they do not provide the same level of antimicrobial activityas the composition as a whole. For example, an enhancer component in theabsence of the antiseptic component may not provide any appreciableantimicrobial activity. The enhancing effect can be with respect to thelevel of kill, the speed of kill, and/or the spectrum of microorganismskilled, and may not be seen for all microorganisms. In fact, an enhancedlevel of kill is most often seen in Gram negative bacteria such asEscherichia coli. An enhancer may be a synergist such that when combinedwith the remainder of the composition, the composition as a wholedisplays an activity that is greater than the sum of the activity of thecomposition less the enhancer component and the composition less theantiseptic component.

The terms “comprises” and variations thereof do not have a limitingmeaning where these terms appear in the description and claims.

As used herein, “a,” “an,” “the,” “at least one,” and “one or more” areused interchangeably. The term “and/or” means one or all of the listedelements (e.g., preventing and/or treating an affliction meanspreventing, treating, or both treating and preventing furtherafflictions).

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2,2.75, 3, 3.80, 4, 5, etc.).

The above summary of the present invention is not intended to describeeach disclosed embodiment or every implementation of the presentinvention. The description that follows more particularly exemplifiesillustrative embodiments. In several places throughout the application,guidance is provided through lists of examples, which examples can beused in various combinations. In each instance, the recited list servesonly as a representative group and should not be interpreted as anexclusive list.

BRIEF DESCRIPTIONS OF THE DRAWINGS

FIG. 1 is a perspective and partially exploded view of an oral care kitaccording to the present invention.

FIG. 2 is a perspective and partially exploded view of an oral care kitaccording to the present invention.

FIG. 3 is a perspective and partially exploded view of an oral care kitaccording to the present invention.

FIG. 4 is a perspective and partially exploded view of an oral care kitaccording to the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention provides a method of moisturizing whiledecolonizing mammalian oral tissue. The present invention also providesan oral care kit and articles used therein for treating oral tissue, forexample, using the present method of moisturizing while decolonizingoral tissue. The method and kit include a moisturizer or substantivemoisturizer composition for moisturizing oral tissue. The moisturizer orsubstantive moisturizer composition can be used in combination with amulti-valent cationic antiseptic, for example, chlorhexidine salts suchas CHG, without reducing the antibacterial activity of the multi-valentcationic antiseptic, or if reduced, the antibacterial activity of themulti-valent cationic antiseptic is reduced to a much lesser extent thanoral tissue moisturizers presently used with a multi-valent cationicantiseptic oral rinse.

An oral tissue moisturizer that is compatible with CHG and in certainembodiments does not leave behind significant residue when repeatedlyapplied allows a user or practitioner a high degree of flexibility inmeeting the individual oral care needs of the user or patient. Sincexerostomia and patient oral health is influenced by factors such ashydration and medications, patients may have vastly different needs fororal moisturization. For example, the moisturizer or substantivemoisturizer can be applied at the same time as the multi-valent cationicantiseptic, such as by including the multi-valent cationic antiseptic aspart of the moisturizer formulation, thereby reducing the number of oraltissue applications. In another example, the moisturizer or substantivemoisturizer can be applied at any time that there is an indication thatthe oral tissue is becoming too dry and could benefit from applicationof a moisturizer. Thus, the moisturizer or substantive moisturizer canbe applied before, during, at the same time as, or after application ofthe multi-valent cationic antiseptic, while still providing or evenmaximizing the antibacterial benefits of the antiseptic, including theeffect of the antiseptic to kill opportunistic microorganisms. In manyinstances, the multivalent cationic antiseptic and moisturizer may beapplied to the oral cavity 4 hours or less apart, for example, less than120 minutes apart. In some instances they may be applied less than 60minutes, 30 minutes, 15 minutes, or even 5 minutes apart. In someinstances they may be applied simultaneously.

Multi-valent cationic antiseptics, such as CHG, can persist on oraltissue in the oral cavity for a number of hours, for example, for up to5 hours. This persistence helps keep pathogenic bacterial counts low inthe oral cavity and helps in the prevention of plaque and gingivitis,which is vital for the care of mechanically ventilated patients inhospitals. For certain embodiments, preferably this benefit can besustained using the methods and kits described herein.

In the present methods, the multi-valent cationic antiseptic is appliedas a composition comprising a solution of the multi-valent cationicantiseptic. For certain embodiments, the solution is an aqueous solutionor a water/alcohol solution of the antiseptic. In other embodiments themultivalent cationic antiseptic is an emulsion such as a water in oil oroil in water emulsion.

Compositions used in conjunction with the multi-valent cationicantiseptic are prepared or selected to prevent or minimize interactionof the antiseptic with a material which precipitates the antisepticand/or which can bind with or otherwise react with the antiseptic andneutralize its antibacterial activity. For certain embodiments,including any one of the above method or kit embodiments or any otherembodiments thereof described herein, any composition applied to tissueor for application to tissue (e.g., moisturizer compositions, de-bridingcompositions, multi-valent cationic antiseptic compositions, other oralcare antiseptic compositions, or another oral care composition)essentially excludes any component which when combined with themulti-valent cationic antiseptic causes a precipitate to form which canbe visibly observed.

In the embodiments described herein, whether or not a precipitate isformed can be determined using Test Method F as described below. Anessentially excluded component is not present or is present in an amountsuch that when combined in that amount with the multi-valent cationicantiseptic no visually observable precipitate is formed. For certain ofthese embodiments, the essentially excluded component is not present.

As used herein, a precipitate is a separate phase, e.g., a solid, a gel,or a liquid that separates out from the antiseptic solution, wherein theprecipitate includes multi-valent cationic antiseptic. When such aprecipitate forms, the amount of multi-valent cationic antiseptic thatremains soluble, and therefore active, may have been reduced. The degreeto which the amount is reduced can be determined by assaying the amountof multi-valent cationic antiseptic in the solution in which it residesusing standard analytical techniques, such a liquid chromatography,light absorbance, and/or other known methods. For example, Test MethodC2 may be used as described below. For certain embodiments, preferablygreater than 40 percent of the original amount of multi-valent cationicantiseptic remains in the solution. For certain of these embodiments,greater than 50, 60, or 70 percent, or even greater than 80, 90, or 95percent of the original amount of multi-valent cationic antisepticremains in the solution. For certain of these embodiments, theessentially excluded component is selected from the group consisting ofpolyanions of polycarboxylates, polysulfonates, polysulfates, andorganic and inorganic polyphosphates; anions of alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; halide salts; andcombinations thereof, wherein the alkyl groups have a chain length ofgreater than 6 carbon atoms and the aryl groups have 6 or more carbonatoms. For certain of these embodiments, the essentially excludedcomponent is not present or present at a concentration less than 0.1percent by weight of the composition, except halide salts which are notpresent or present at a concentration not greater than 0.2 wt-% byweight of the composition. For certain of these embodiments, theessentially excluded component is selected from the group consisting ofsodium saccharin, potassium sorbate, sodium benzoate, potassiumchloride, sodium chloride, phosphoric acid, citric acid, sodiumcarboxymethylcellulose, carbomers, such as Carbomer 954, and glycerylpolymethacrylate. Alternatively or additionally, for certain of theseembodiments, any composition applied to the oral tissue or forapplication to the oral tissue, for example, the moisturizercomposition, is such that a log reduction in the number of viablebacterial cells of at least 2 is provided when 10⁶ cfu of Pseudomonasaeruginosa (ATCC 27853) are combined with a mixture of 1.1 g of thecomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B. For certain embodiments, including the aboveembodiments, a log reduction in the number of viable bacterial cells ofat least 3, preferably at least 4 or 5 is provided.

For certain embodiments, including any one of the above method or kitembodiments or any other embodiments thereof described herein, themoisturizer or substantive moisturizer composition is such that at least35 percent, preferably at least 40 percent, more preferably greater than40 percent, and for certain embodiments, preferably greater than 50percent, more preferably greater than 60 percent, more preferablygreater than 70 percent, and even more preferably greater than 80percent of the multi-valent cationic antiseptic remains soluble when themulti-valent cationic antiseptic is combined with the moisturizer orsubstantive moisturizer composition in a weight ratio of 1 partmoisturizer or substantive moisturizer composition to 1 partmulti-valent cationic antiseptic composition containing the multi-valentcationic antiseptic. The amount of the multi-valent cationic antisepticthat remains soluble can be determined, for example, by measuring theamount that can be recovered from a mixture of the moisturizer orsubstantive moisturizer composition and the multi-valent cationicantiseptic within 4 hours with a mixture of water and methanol accordingto Test Method C. For certain embodiments, including any one of theabove method or kit embodiments or any other embodiments thereofdescribed herein, the moisturizer or substantive moisturizer compositionis such that at least 35 percent, preferably at least 40 percent, morepreferably greater than 40 percent of the multi-valent cationicantiseptic remains soluble and can be recovered from a mixture of themoisturizer or substantive moisturizer composition and the multi-valentcationic antiseptic within 4 hours with a mixture of water and methanolaccording to Test Method C. For certain of these embodiments, greaterthan 50 percent, greater than 60 percent, greater than 70 percent, orgreater than 80 percent of the multi-valent cationic antiseptic remainssoluble and can be recovered. It is understood, however, that thesolvent system should be considered and optimized for each compositionto ensure that control samples of known cationic antisepticconcentration in the same range as the test sample achieve completerecovery of the cationic antiseptic. For example, water and acetonitrilemay also be used instead of water and methanol, and trifluoroacetic acid(TFA), formic acid, ammonium acetate, or ammonium formate may be usedwith these solvent mixtures. One skilled in the art will know how tomodify the solvent system.

For certain embodiments, including any one of the above method or kitembodiments or any other embodiments thereof described herein, themoisturizer or substantive moisturizer composition essentially excludesa component selected from the group consisting of polyanions such aspolycarboxylates, polysulfonates, polysulfates, and polyphosphates;chelators; inorganic buffers; anions such as alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; and combinationsthereof. Alkyl groups referred to here include those having a chainlength of greater than four carbon atoms, preferably alkyl groups of 6or more carbon atoms, preferably greater than 6 carbon atoms. Arylgroups referred to here include those having 6 or more carbon atoms.Anions including such alkyl and aryl groups, which do not includehydroxyl groups or other polar solubilizing groups, may precipitate themulti-valent cationic antiseptic from solution. “Polyanion” as usedherein is a small molecule oligomer, or polymer having, on average, atleast two ionic groups (e.g., carboxylate, sulfate, sulfonate, orphosphate group) per molecule. For certain embodiments, halide salts ata concentration greater than 1 wt-%, 0.5 wt-%, or 0.2 wt-% by weight ofthe composition in a combination of the multi-valent cationic antisepticand the moisturizer or substantive moisturizer composition are furtheressentially excluded. For certain of these embodiments, the essentiallyexcluded component is selected from the group consisting of sodiumsaccharin, potassium sorbate, sodium benzoate, potassium chloride,sodium chloride, phosphoric acid, citric acid, sodiumcarboxymethylcellulose, carbomers, such as Carbomer 954, and glycerylpolymethacrylate. Essentially excluded components are not present or arepresent in amounts which allow for at least a 2 log reduction determinedaccording to Test Method B. Alternatively, or in addition, essentiallyexcluded components are not present or are present in amounts such thatat least 35 percent, preferably at least 40 percent, more preferablygreater than 40 percent, of the multi-valent cationic antiseptic remainssoluble and can be recovered from a mixture of the moisturizer orsubstantive moisturizer composition and the multi-valent cationicantiseptic within 4 hours with a mixture of water and methanol accordingto Test Method C. For certain of these embodiments, greater than 50percent, greater than 60 percent, greater than 70 percent, or greaterthan 80 percent of the multi-valent cationic antiseptic remains solubleand can be recovered. For certain of these embodiments, the essentiallyexcluded components are not present.

For certain embodiments, including any one of the above method or kitembodiments or any other embodiments thereof described herein,preferably when the moisturizer or substantive moisturizer compositionincludes an anionic compound, the anionic compound is such that a logreduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas auerginosa are combined with amixture of 1.1 g of the moisturizer or substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B. Alternatively, or in addition, preferablywhen the moisturizer or substantive moisturizer composition includes ananionic compound, the anionic compound is such that greater than 40percent of the multivalent cationic antiseptic is soluble when themulti-valent cationic antiseptic and the moisturizer or substantivemoisturizer composition are combined. Preferably greater than 50percent, greater than 60 percent, greater than 70 percent, or greaterthan 80 percent of the multi-valent cationic antiseptic remains soluble.Here, if possible, the anionic compound is selected and used in anamount such that these conditions are met. For certain of theseembodiments, the anionic compound is selected from the group consistingof polyanions such as polycarboxylates, polysulfonates, polysulfates,and polyphosphates; chelators; inorganic buffers; anions such asalkylsulfates, arylsulfates, alkylsulfonates, arylsulfonates,alkylcarboxylates, arylcarboxylates, alkylphosphates, arylphosphates;and combinations thereof. Alkyl groups referred to here include thosehaving a chain length of greater than six carbon atoms. However, alkylgroups of four or less carbon atoms may increase the likelihood that theabove amounts of multi-valent cationic antiseptic remains soluble in thepresence of such anions. Aryl groups referred to here include thosehaving 6 or more carbon atoms. Anions including such alkyl and arylgroups, which do not include hydroxyl groups or other polar solubilizinggroups, may precipitate the multi-valent cationic antiseptic fromsolution. “Polyanion” as used herein is a small molecule oligomer, orpolymer having, on average, at least two ionic groups (e.g.,carboxylate, sulfate, sulfonate, or phosphate group) per molecule. Forcertain embodiments, the group from which the anionic compound isselected further includes halide salts at a concentration greater than0.2 wt-% by weight of the composition.

For certain embodiments, any other composition described herein and usedin combination with the multi-valent cationic antiseptic, for example, ade-briding composition, also essentially excludes these materials andcomponents.

For optimal multi-valent cationic antiseptic activity, for example,maximizing antimicrobial effectiveness, the pH of the moisturizer orsubstantive moisturize is preferably in the mildly acidic toapproximately neutral range. For certain embodiments, including any oneof the above embodiments, the moisturizer or substantive moisturizercomposition has a pH of 3 to 8 or 4 to 8. For certain of theseembodiments, the pH is at least 4.5, at least 5, or at least 6. Forcertain of these embodiments, the pH is not greater than 7.5, preferablynot greater than 7. For certain of these embodiments, the pH is 4.5 to7, preferably 6 to 7.

Because of the presence of saliva and/or mucus secretions as well asother medicaments or compositions that may be administered in the oralenvironment, the moisturizer is preferably substantive to resist beingwashed or dislodged from the oral tissue for a period of time. Forcertain embodiments, preferably at least a portion of the appliedsubstantive moisturizer remains at the site of application for at least1 hour, at least 2 hours, or more preferably at least 4 hours.Substantivity may by evaluated using Test Method E described below.Relatively high viscosities are preferred to reduce migration as well asto provide substantivity (resistance to removal by fluids) to ensuremoisturization for long periods of time. In certain embodiments,including any one of the above embodiments, the substantive moisturizercomposition has a viscosity of at least 20 centipoise (cps), preferablyat least 50 cps, preferably at least 100 cps, more preferably at least500 cps. For certain of these embodiments, the substantive moisturizercomposition has a viscosity of at least 1,000 cps, more preferably atleast 10,000 cps. Most preferred compositions have viscosities of atleast 20,000 cps, more preferably in excess of 50,000 cps. For certainembodiments, the viscosity can be at least 100,000 cps or even at least1,000,000. These viscosities can be conveniently measured by theViscosity Test (Test Method A) described herein. Compositions meet theseviscosity values at 22-25° C., and in certain embodiments even afterheating to 32° C., 35° C. or as high as 37° C., so that when in contactwith mammalian tissue the compositions remain substantive. For certainof these embodiments, preferably the substantive moisturizer compositionincludes a hydrophobic component (e.g., as described below) and/or apolyhydroxy compound and can be spread evenly across the tissue.Clearly, it is also important that the composition wet the tissue inorder to easily coat the tissue without dewetting. This can be criticalto achieving substantivity. Wetting can be achieved by adjusting thevehicle components and/or addition of surfactant(s).

In order to further enhance substantivity of the compositions, forcertain embodiments, polycationic polymers are included in themoisturizer composition. These are not only compatible with themultivalent cationic antiseptic and improve retention by increasingviscosity, but they also increase retention or substantivity byionically binding with the oral tissue.

Moreover, for certain embodiments, hydrophobic water insolublecomponents are included to increase retention. For example, high oil inwater emulsions or water in oil emulsions can resist removal frommucosal tissue due to the water insoluble nature of the oil. Suitableoils include any of the hydrophobic emollients and emulsifiers disclosedin U.S. Pat. No. 6,562,360. In particular, use in the oral cavity ofthose emollients and emulsifiers that are approved for use as foodadditives are particularly preferred. For example, C8 to C18 mono-, di-and tri-esters of glycerin and propylene glycol may be used as well as avariety of edible oils such as vegetable oils.

Compositions comprising the multi-valent cationic antiseptic, alone orin combination with the moisturizer or substantive moisturizercomposition, can provide at least a 2 log reduction in the number ofviable bacterial cells of at least one type of bacteria. Bacterialreduction is generally reported as log₁₀ reduction determined by thedifference between the log₁₀ of the initial inoculum count and the log₁₀of the inoculum count after exposure to the multi-valent cationicantiseptic. For certain embodiments, compositions comprising themulti-valent cationic antiseptic included in the methods and kits of thepresent invention provide an average of at least a 2 log reduction in atest bacteria 30 minutes, preferably in 10 minutes, more preferably in2.5 minutes. For certain of these embodiments, compositions comprisingthe multi-valent cationic antiseptic, alone or in combination with themoisturizer or substantive moisturizer composition, provide an averageof at least a 3 log reduction, preferably at least a 4 log reduction inthe test bacteria.

A bacterial assay can be used to determine when a composition comprisinga multi-valent cationic antiseptic alone or in combination with amoisturizer or substantive moisturizer composition provides sufficientantimicrobial activity. One readily performed assay involves exposing aselected known or readily available viable microorganism strain, such asEnterococcus spp., Aspergillus spp., Escherichia spp. (e.g., E. coli),Staphylococcus spp. (e.g., Staphylococcus aureus), Streptococcus spp.(e.g., Streptococcus pneumonia), Pseudomonas spp. (e.g., Pseudomonasaeruginosa), Enterobacter spp., or Salmonella spp., or othermicroorganism such as Haemophilus influenza or Acinetobacter baumannii,to a test composition at a predetermined bacterial burden level in aculture media at an appropriate temperature. This may be convenientlycarried out using the Test Method B described in the Examples Section.Briefly, in Test Method B, approximately 10⁶ cfu's are inoculated into amulti-valent cationic antiseptic composition, or a moisturizercomposition mixed with a multi-valent cationic antiseptic composition,or a moisturizer composition which includes a multi-valent cationicantiseptic. After incubation for a specific time period, the mixture isneutralized and enumerated by dilution plating.

Compositions comprising the multi-valent cationic antiseptic alone or incombination with the moisturizer or substantive moisturizer compositionmay provide residual antimicrobial efficacy by maintaining an averagelog reduction of at least 1 log, more preferably at least 1.5 log, andeven more preferably at least 2 log, for at least 1 hour, morepreferably at least 2 hours, and even more preferably at least 4 hoursafter application to oral tissue.

Multi-valent cationic antiseptics, such as chlorhexidine, kill bothgram-positive and gram-negative microbes. In addition, they are activeagainst lipid enveloped viruses and fungi. At least one mechanism ofaction is believed to be membrane disruption. Examples of relevantmicroorganisms against which the antiseptics are active, although notnecessarily those normally encountered in the oral cavity, includeStaphylococcus spp., Streptococcus spp., Pseudomonas spp., Enterococcusspp., and Esherichia spp., Aspergillus spp., Fusarium spp.,Acinetobacter spp., and Candida spp. Particularly virulent organismsinclude Staphylococcus aureus (including resistant strains such asMethicillin Resistant Staphylococcus Aureus (MRSA), Staphylococcusepidermidis, Streptococcus mutans, Streptococcus pneumoniae,Enterococcus faecalis, Vancomycin Resistant Enterococcus (VRE),Pseudomonas aeruginosa, Escherichia coli, Aspergillus niger, Aspergillusfumigatus, Aspergillus clavatus, Fusarium solani, Fusarium oxysporum,Fusarium chlamydosporum, Candida albicans, Candida glabrata, and Candidakrusei. For certain embodiments, those microorganisms relevant to theoral cavity and oral tissue, for example, of a mechanically ventilatedsubject, include Staphylococcus aureus, Streptococcus pneumonia,Pseudomonas aeruginosa, Haemophilus influenza and Acinetobacterbaumannii, and Enterobacter spp.

For certain embodiments, including any one of the above embodiments, themulti-valent cationic antiseptic is selected from the group consistingof biguanides, bisbiguanides, polybiguanides, polymeric quaternaryammonium compounds, and combinations thereof. Biguanides include thefollowing 2-carbamimidoylguanidine structure of formula (I):R¹R²N—C(═NH)—NH—C(═NH)—NR³R⁴  (I)wherein at least one of R¹, R², R³, and R⁴ is an alkyl, aryl, orarylalkyl group, and any remaining R¹, R², R³, or R⁴ groups arehydrogen.

Bisbiguanides include the following bis(2-carbamimidoylguanidine)structure of formula (II):R¹R²N—C(═NH)—NH—C(═NH)—NH—X—HN—C(═NH)—NH—C(═NH)—NR³R⁴  (II)wherein at least one of R¹, R², R³, and R⁴ is an alkyl, aryl, orarylalkyl group, and any remaining R¹, R², R³, or R⁴ groups arehydrogen, and X is a divalent connecting group, for example astraight-chain or branched C₃₋₁₀ alkylene group, optionally interruptedwith —O—, —S—, or arylene (e.g., phenlyene, naphthylene), preferablystraight-chain C₄₋₈ alkylene preferably straight-chain hexylene.

At least one of R¹ and R² and at least one of R³ and R⁴ is preferablyhydrogen. Alkyl groups include, for example, C₁₋₁₈ alkyl groups,preferably C₁₋₈ alkyl groups. Aryl groups include C₆₋₁₀ aryl groups,preferably phenyl groups. Arylalkyl groups include any combination ofthese alkyl and aryl groups, for example, benzyl and 2-phenylethyl. Anyof these groups may be substituted with one or more halo, nitro, C₁₋₄alkyl, C₁₋₄ alkoxy, C₄₋₉ cycloalkyl, or a combination thereof.

Polybiguanides include the following polymeric structure of formula(III) wherein X is as described above; Z is a terminal group such as anamino group or salt thereof, a dicyandiamido group or a cyanoguanidinogroup; and n is at least 3 and not more than about 50, preferably atleast 4 and not more than about 40, more preferably at least 5 and notmore than 20:Z—[X—HN—C(═NH)—NH—C(═NH)—NH-]_(n)X—Z  (III)

Examples of biguanides of formula (I) include but are not limited toMetformin (R¹ and R²=methyl), Buformin (R¹=n-butyl, Phenformin(R₁=2-phenylethyl), and the like. Examples of bisbiguanides of formula(II) include but are not limited to chlorhexidine (X is —(CH₂)₆—, and R¹and R³ are 4-chlorophenyl) and alexidine(1,1′-hexamethylene-bis[5-(2-ethylhexyl)biguanide]) and their varioussalts such as the digluconate, diacetate, dimethosulfate, and dilactatesalts as well as combinations thereof. Examples of polybiguanidesinclude but are not limited to PHMB (poly(hexamethylenebiguanide)) andsalts thereof. In one preferred form, PHMB is commercially available asCosmocil CQ from Arch Chemicals Inc., Smyrna Ga.

Polymeric quaternary ammonium compounds include polymers havingquaternary amine groups with at least one alkyl or aralkyl chain of atleast 6 carbon atoms and preferably as least 8 carbon atoms. Thepolymers may be linear, branched, hyperbranched or dendrimers. Examplesof antimicrobial polymeric quaternary amine polymers include but are notlimited to quaternary ammonium functionalized dendrimers such as thosedescribed in U.S. Pat. No. 6,440,405; polymers which are thepolymerization product of quaternary ammonium functional (meth)acrylatemonomers such as those described in U.S. Pat. No. 5,408,022; polyethers,polycarbonates, and polyurethanes prepared from quaternary ammoniumfunctional diols such as those described in U.S. Pat. No. 5,084,096; andthe like

Any soluble salt of the multi-valent cationic antiseptic, including theabove described salts, may be used. For example, where hydrochloridesalts are soluble, such salts are suitable.

“Soluble” as used herein with respect to the multi-valent cationicantiseptic and/or salts thereof refers to solubility in a composition,for example, an aqueous fluid, above the minimum inhibitoryconcentration (MIC) of the treatment microorganism. If the solubilitylimit is less than the MIC, treatment may be ineffective. Preferably thesolubility exceeds the minimum bacteriacidal concentration (MBC).

For certain embodiments, including any one of the above embodiments,preferably the multi-valent cationic antiseptic is a bisbiguanide or apolybiquanide. For certain of these embodiments, the multi-valentcationic antiseptic is chlorhexidine or PHMB. For certain of theseembodiments, the multi-valent cationic antiseptic is PHMB.Alternatively, for certain of these embodiments, the multi-valentcationic antiseptic is chlorhexidine. The multi-valent cationicantiseptic may be present as the free base, but is preferably present asa soluble salt. For example, chlorhexidine may be present as the freebase but is preferably present as a disalt of acetate, gluconate,lactate, methosulfate (CH₃OSO₃ ⁻), or combinations thereof. These saltsall have solubility limits in water in excess of 1 g/100 ml. Forexample, the solubility limit of the digluconate salt is 20 g/100 ml andthat of the diacetate is 1.9 g/100 ml. For certain of these embodiments,preferably the multi-valent cationic antiseptic is chlorhexidinedigluconate (CHG). In one alternative, preferably the multi-valentcationic antiseptic is the hydrochloride of PHMB.

The multi-valent cationic antiseptics are dissolved in an aqueouscarrier, for example water or water and an alcohol, a non-aqueouscarrier, or a combination thereof and protected from light. Protectionfrom light and use of a non-aqueous carrier may help reduce thedegradation of susceptible antiseptic compounds over time. When used incompositions comprising less than about 20% by weight water, theseantiseptics are preferably formulated with a hydrophilic carrier thatsolubilizes the antiseptic. Examples of suitable solvents for manymultivalent cationic antiseptics, including chlorhexidine gluconate,include glycols (compounds having at least two hydroxyl groups permolecule) such as PEGs having a molecular weight below 2000 andpreferably less than 1000 and most preferably less than about 800daltons; glycerin and polyglycerols, propylene glycol, dipropyleneglycol, tripropylene glycol, polypropylene glycol, ethyleneoxide/propylene oxide random or block copolymers, trimethylolpropane,pentraerythritol, sorbitol, panetothenol, glucuronolactone, gluconicacid, and the like as well as other polar solvents such as N-methylpyrrolidone, propylene carbonate, butyrolactone and the like.

Care may be taken when formulating chlorhexidine as well as othermulti-valent cationic antiseptic compounds to avoid inactivation bysequestering it in micelles which may be formed by incorporation ofsurfactants and/or emulsifiers (for example, certain nonionicsurfactants). Some examples of formulations that may be used includehydrophilic ointments; aqueous solutions thickened with polymericthickeners that are either surfactant free or contain surfactants thatdo not reduce the activity of the CHG, such as certain poloxamers; andointments comprising a major amount of a hydrophobic component andpreferably further comprising a hydrophilic component.

The multi-valent cationic antiseptics, such as chlorhexidine, are verybasic and capable of forming multiple ionic bonds with anionicmaterials. For this reason, the multi-valent cationic antisepticcompositions, as well as the moisturizer or substantive moisturizercompositions and other compositions used in combination with theantiseptic compositions are preferably free of anionic compounds thatcan result in precipitation of the antiseptic. Also, thickener systems,if present, are preferably based on non-ionic and/or cationic polymersor emulsifiers. Anionic surfactants useful, for example, as wettingagents, may also need to be avoided. Certain zwitterionic, very watersoluble, or non-precipitating anionic emulsifiers and surfactants may beuseful. Although halide salts were previously believed to cause CHG toprecipitate, it has now been found that salts, such as sodium chloridemay be used at levels up to 0.2 percent by weight of the composition.Therefore, if a system includes CHG or other multi-valent cationicantiseptic, and needs to comprise salts for stability or other purposes,the salt should be evaluated for compatibility with the multi-valentcationic antiseptic. For example, the inhibitory levels of certainreagents like salt or anionics can be different from CHG for a polymericguanide such as PHMB and would require testing. However, gluconate saltssuch as triethanolamine gluconate or sodium gluconate, can be used withCHG. Furthermore, if an additional antiseptic is incorporated into thecomposition it is preferably non-ionic or cationic. If it is cationicthe counter ion should be compatible with both antiseptics ensuringsolubility of both. Attention may be paid to the pKa, pH, acidequivalents, and solubility of polymer in question when potentiallyinhibitory compounds are used in the formulation. However, thesecriteria may be insufficient to determine if sufficient kill can beobtained when a cationic antiseptic is used with a moisturizer orsubstantive moisturizer.

For certain embodiments, including any one of the above embodiments, themulti-valent cationic antiseptic is included in a composition at asufficient concentration such that when applied to mammalian tissue foran adequate time, for an adequate frequency, and in an adequate dose theantiseptic can provide at least a 2 log reduction, decolonize, oreradicate at least one microorganism from the oral tissue. For certainof these embodiments, the concentration is at least 0.05 weight percent(wt-%). For example, for certain embodiments, the moisturizer orsubstantive moisturizer composition contains 0.05 wt-% of a multi-valentcationic antiseptic as a preservative. For certain of these embodiments,the concentration is at least 0.1 wt-%. For certain of theseembodiments, the multi-valent cationic antiseptic is included in acomposition at a concentration of no greater than 2 wt-%, no greaterthan 1 wt-%, no greater than 0.5 wt-%, no greater than 0.4 wt-%, or nogreater than 0.20 wt-%. For certain of these embodiments, themulti-valent cationic antiseptic is included in a composition comprisinga solution of the multi-valent cationic antiseptic at 0.05 to 0.4 weightpercent. For certain of these embodiments, the multi-valent cationicantiseptic is included in a composition comprising a solution of themulti-valent cationic antiseptic at 0.1 to 0.2 weight percent. Forcertain of these embodiments, the multi-valent cationic antiseptic isincluded in a composition comprising a solution of the multi-valentcationic antiseptic at 0.12 weight percent in water and alcohol. In oneexample, the composition is commercially available as PERIDEX (0.12 wt-%chlorhexidine gluconate, 3M Health Care, St. Paul, Minn.).

The multi-valent cationic antiseptics may be used alone, in combination,or with other antiseptics in order to effectively kill microorganisms onoral tissue. Additional antiseptics for use with the multi-valentcationic antiseptic include peroxides, antimicrobial natural oils, andcompatible combinations thereof as provided in U.S. Patent ApplicationPublication No. 2006/0051384 A1; diphenyl ethers, phenols, halogenatedphenols, bisphenols, resorcinols and its derivatives, anilides, andcombinations thereof, provided in U.S. Patent Application PublicationNo. 2006/0052452 A1. Also, antimicrobial lipid antiseptics mayadditionally be used. Such antimicrobial lipids include(C7-C14)saturated fatty acid esters of a polyhydric alcohol,(C8-C22)unsaturated fatty acid esters of a polyhydric alcohol,(C7-C14)saturated fatty ethers of a polyhydric alcohol,(C8-C22)unsaturated fatty ethers of a polyhydric alcohol, andalkoxylated derivatives thereof, or combinations thereof, wherein thealkoxylated derivative has less than 5 moles of alkoxide per mole ofpolyhydric alcohol; with the proviso that for polyhydric alcohols otherthan sucrose, the esters comprise monoesters and the ethers comprisemonoethers, and for sucrose the esters comprise monoesters, diesters, orcombinations thereof, and the ethers comprise monoethers, diethers, orcombinations thereof. Useful antiseptics of this class are furtherdescribed in U.S. Patent Application Publication No. 2005/0058673. Asused herein the term “fatty” refers to alkyl and alkylene hydrocarbonchains of odd or even number of carbon atoms from C6-C18.

Alternatively, the antimicrobial lipid can be a (C8-C12)fatty alcoholester of a (C2-C8)hydroxycarboxylic acid (also often referred to as a(C2-C8)hydroxycarboxylic acid ester of a (C8-C12)fatty alcohol), a(C8-C22)mono- or poly-unsaturated fatty alcohol ester of a(C2-C8)hydroxycarboxylic acid (also often referred to as a(C2-C8)hydroxycarboxylic acid ester of a (C8-C22)mono- orpoly-unsaturated fatty alcohol), or alkoxylated derivatives thereof. Thealkoxylated derivatives have less than 5 moles of alkoxide per mole ofpolyhydric alcohol or hydroxy acid. The hydroxycarboxylic acid moietycan include aliphatic and/or aromatic groups. For example, fatty alcoholesters of salicylic acid are possible.

As used herein, a “fatty alcohol” is an alkyl or alkylene monofunctionalalcohol having an even or odd number of carbon atoms and a “fatty acid”is an alkyl or alkylene monofunctional carboxylic acid having an even orodd number of carbon atoms.

Cationic antiseptic compositions may have a persistently bitter taste.It has now been found that certain non-ionic sweetening compounds can beused together with the multi-valent cationic antiseptic to significantlyreduce this bitter taste without significantly diminishing antisepticactivity. We have found that anionic sweeteners employed in thesecompositions previously, such as sodium saccharin, can precipitatecationic actives such as chlorhexidine gluconate. We believe this wouldbe true for many cationic antiseptics. For certain embodiments,including any one of the method or oral care kit embodiment describedherein, the composition including the multi-valent cationic antisepticfurther comprises a sweetener selected from the group consisting ofsucralose, aspartame, sugars and sugar alcohols including but notlimited to xylose, sucrose, maltose, mannose, glucose, xylitol,sorbitol, mannitol, erythritol, maltitol, lactitol, and a combinationthereof.

For certain embodiments, compositions comprising the multi-valentcationic antiseptic also include at least one additional componentselected from the group consisting of enhancers, surfactants,hydrophilic compounds, hydrophobic compounds, and combinations thereof.

Compositions used in the present method and kit can be applied withswabs, cloth, sponges, foams and non-woven and paper products (e.g.,paper towels and wipes), for example where they are used to deliver asignificant portion of the antiseptic composition to the oral tissue. By“significant portion” it is meant that enough composition is applied andallowed to remain on the tissue when applied in a dose, at a frequency,and in an amount sufficient to reduce or eliminate the microorganisms onor in the tissue.

Compositions used in the present method and kit are physically stable.As defined herein “physically stable” compositions are those that do notsignificantly change due to substantial precipitation, crystallization,phase separation, and the like, from their original condition duringstorage at 25° C. for at least 3 months, and preferably for at least 6months. Particularly preferred compositions are completely physicallystable if a 10-milliliter (10-ml) sample of the composition when placedin a 15-ml conical-shaped graduated plastic centrifuge tube (Corning)and centrifuged at about 2275×g (e.g. 3,000 revolutions per minute (rpm)for 10 minutes using a Labofuge B, model 2650 manufactured by HeraeusSepatech GmbH, Osterode, West Germany) or similar centrifuge at acentrifugal force of 2275×g has no visible phase separation in thebottom or top of the tube. Phase separation of less than 0.5 ml is alsoconsidered stable as long as there is no other sign of physicalseparation in the sample.

Compositions used in the present method and kit exhibit good chemicalstability. This can be a concern with compounds that may hydrolyze orundergo heat and/or light degradation such as chlorhexidine. The mostpreferred compositions retain an average of at least 97% of theantiseptic component after aging for 4 weeks at 40° C. in a sealedcontainer beyond the initial 5-day equilibration period at 25° C. Thepercent retention is understood to mean the weight percent of antisepticcomponent retained. This is determined by comparing the amount remainingin a sample aged (i.e., aged beyond the initial 5-day equilibrationperiod) in a sealed container that does not cause degradation, to theactual measured level in an identically prepared sample (preferably fromthe same batch) and allowed to sit at 25° C. for five days. The level ofantiseptic component is preferably determined using gas chromatographyor high performance liquid chromatography using appropriate standardsand controls.

In the present methods, the multi-valent cationic antiseptic is appliedas a composition comprising a solution of the multi-valent cationicantiseptic. For certain embodiments, the solution is an aqueous solutionor a water/alcohol solution of the antiseptic.

As indicted above, the multi-valent cationic antiseptic is included in acomposition comprising a solution of the multi-valent cationicantiseptic, and for certain embodiments, the solution is an aqueoussolution or a water/alcohol solution of the antiseptic. The compositionmay additionally include various other materials as described herein.Alternative compositions where the multi-valent cationic antiseptic isdissolved in or mixed with a non-aqueous hydrophilic material are alsocontemplated.

The moisturizer or substantive moisturizer composition may be used orprovided in various forms including, for example, hydrophobic ointments,oil in water emulsions, water in oil emulsions, thickened aqueous gels,and hydrophilic gels.

Hydrophobic compositions include a hydrophobic base or vehicle (e.g.,petrolatum, insoluble oils, thickened or gelled water insoluble oils andthe like) and may include a minor amount of a water-soluble phase, whichwould include the multi-valent cationic antiseptic if present.Acceptable salts, surfactants, emulsifiers, humectants and/or othercomponents may also be included. Care must be taken to ensure that thecomposition does not degrade or negatively effect the endotracheal tubeused for ventilation or other medical devices that may be in contact orin proximity to the mucosal tissue. Certain hydrophobic components candegrade plasticized PVC which is commonly used as endotracheal tubematerial. Preferably the compositions do not negatively effect naturalrubber latex or nitrile gloves.

Oil in water emulsion compositions include a discrete phase of ahydrophobic component and a continuous aqueous phase comprising waterand optionally one or more polar hydrophilic carriers, where either orboth phases include the multi-valent cationic antiseptic if present.Acceptable salts, surfactants, emulsifiers, humectants, and/or othercomponents may also be included. These emulsions may comprise acceptablewater-soluble or water swellable polymers as well as one or moreemulsifiers that help to stabilize the emulsion.

Water in oil emulsion compositions include a continuous phase of ahydrophobic component and an aqueous phase comprising water andoptionally one or more polar hydrophilic carriers as well as acceptablesalts or other components, where the multi-valent cationic antiseptic ifpresent is in either or both phases. Acceptable salts, surfactants,emulsifiers, humectants and/or other components may also be included.These emulsions may comprise oil soluble or oil swellable polymers andone or more emulsifiers, as well as inorganic salts such as magnesiumsulfate, that help to stabilize the emulsion.

Thickened aqueous gel compositions include an aqueous phase, which wouldinclude the multi-valent cationic antiseptic if present, that has beenthickened to achieve a sufficiently high viscosity as described above,for example, a viscosity of at least 10 cps and preferably at least 20cps. Viscosities of at least 50 cps, at least 100 cps, at least 250 cps,or at least 500 cps may also be preferred. The viscosity is determinedusing the Viscosity Test described herein. These compositions arethickened by suitable natural, modified natural, or synthetic polymersas described below. The thickened aqueous gels can also be thickenedusing suitable emulsifiers such as alkyl alcohols and polyethoxylatedalkyl chain surfactants that effectively thicken the composition.Examples include the Polawax, Behenyl TMS, Crodaphos CES, Cosmowax, andCrothix systems from Croda Inc.

Hydrophilic gel compositions include a continuous phase comprised of atleast one water soluble hydrophilic component other than water. Theformulations may contain water up to 90% by weight. The higherconcentrations may be suitable in some compositions. Suitablehydrophilic components are described below under the heading“Hydrophilic Component.” For certain embodiments, suitable hydrophiliccomponents include one or more glycols (such as glycerin, propyleneglycol, butylenes glycol, etc.), polyethylene glycols (PEG), random orblock copolymers of ethylene oxide, propylene oxide, and/or butylenesoxide, polyalkoxylated surfactants having one or more hydrophobicmoieties per molecule, silicone copolyols, as well as combinationsthereof. One skilled in the art will recognize that the level ofethoxylation must be sufficient to render the hydrophilic componentwater-soluble or water dispersible at 23° C.

As indicated above, the present methods and kits can provide asignificant advancement in antimicrobial effectiveness as well asflexibility in applying the moisturizer composition as needed by apatient. Because the moisturizer or substantive moisturizer compositionmaintains the antimicrobial effectiveness of the multi-valent cationicantiseptic, the moisturizer can be applied at any time in the presenceof the antiseptic. For certain embodiments, including any one of theabove method embodiments, the moisturizer or substantive moisturizercomposition is applied after applying the cationic antiseptic.Alternatively, for certain of these embodiments, the moisturizer orsubstantive moisturizer composition is applied before applying thecationic antiseptic. For certain of these embodiments, the moisturizeror substantive moisturizer composition and the multi-valent cationicantiseptic are applied within 12 hours of each other. For certain ofthese embodiments, the moisturizer or substantive moisturizercomposition and the multi-valent cationic antiseptic are applied within4 hours of each other. For certain of these embodiments, preferably themoisturizer or substantive moisturizer composition and the multi-valentcationic antiseptic are applied within less than 120, 60, or 30 minutesof each other. For certain of these embodiments, the moisturizer orsubstantive moisturizer composition is applied at the same time asapplying the multi-valent cationic antiseptic. For certain of theseembodiments the moisturizer or substantive moisturizer compositioncontains the multi-valent cationic antiseptic, and the moisturizer andantiseptic are applied simultaneously.

Certain commercially available mouth moisturizing products used to treatventilated patients have been found to include components that havefilm-forming properties and often leave behind a peelable, unabsorbedfilm as the product dries on the tissue upon which it is applied. Thisis particularly problematic for mouth moisturizers used in a hospitalsetting on ventilated patients, where mouth moisturizers are used bothinside of the patient's mouth and on the lips. It has been found that assuch moisturizers dry and are re-applied, a buildup of residue can givethe appearance of dried, peeling lips. This can give an appearance orimpression, for example, to hospital visitors, that patients are notproperly cared for. Furthermore, once the film cracks and peels themoisturization “barrier” can be lost.

It has also now been found that such moisturizers shrink to aconsiderable extent when dried. Shrinkage is believed to contribute tothe undesirable appearance. For certain embodiments, including any oneof the above embodiments of the method and kit, levels and combinationsof multi-valent cationic antiseptic-compatible thickeners, humectants,and excipients are combined such that peel-able film formation by themoisturizer or substantive moisturizer composition is minimized and theproduct is more esthetically pleasing when dried on oral tissue, such asthe lips. For certain of these embodiments, the moisturizer orsubstantive moisturizer composition has a shrinkage of less than 10percent when dried under ambient conditions for 2 hours. For certainembodiments, ambient conditions include 22-25° C. and 30 to 50 percentrelative humidity. For certain embodiments, ambient conditions include25° C. and 30 percent relative humidity. Shrinkage is easily determinedby coating a substrate of known area, allowing the composition to dryand measuring the area of the dried composition, for example, accordingto Test Method D. A dried film of at least 50 microns and preferably notmore than 350 microns in thickness may be used. Shrinkage measurementsshould be done on a surface that allows the composition to debond if itis inclined to do so upon drying. This typically means it should be doneon the lowest surface energy substrate that allows one to put down auniform coating without dewetting.

For certain of these embodiments, the moisturizer or substantivemoisturizer composition when dried on a surface, such as the surface ofa clear plastic petri dish, does not form a self-supporting film, thatis, it cannot be peeled from the surface in a single piece. For certainof these embodiments, the dried moisturizer or substantive moisturizercomposition cannot be peeled from the surface in a piece having a sizegreater than 30 percent of the area of the dried moisturizer orsubstantive moisturizer composition. For certain embodiments,self-supporting means that when the composition is dried on a suitablesurface such as a release liner of suitably low surface energy, a filmso formed can be removed from the release liner in a single piece andthe film is capable of supporting its own weight. Evaluation for suchcharacteristics may be carried out using Test Method D described below.Sufficient coating is typically applied to ensure a dried film of atleast 50 microns and preferably not more than 350 microns in thickness.

The moisturizer or substantive moisturizer composition is applied in anamount sufficient to cover oral tissue that is susceptible to becomingexcessively dry and compromised. For certain embodiments, including anyone of the above method embodiments, the moisturizer or substantivemoisturizer is applied in an amount of 1 to 10 grams per application.More may be applied if any excess is removed.

As indicated above, such oral tissue includes, for example, lips,mucosal tissue, tongue, and teeth. For certain embodiments, includingany one of the above embodiments, the oral tissue is oral mucosaltissue. For certain of these embodiments, the oral mucosal tissue isselected from the group consisting gingiva, buccal mucosa, the floor ofthe mouth, the hard palate, the soft palate, the dorsal tongue, thelateral tongue, the ventral tongue, an oropharyngeal surface, andcombinations thereof.

Subjects who may benefit from the present methods include any who have acondition of dry oral tissue. However, mechanically ventilated patients,such as those in a hospital setting, may receive significantly improvedcare. For certain embodiments, including any one of the above methodembodiments, the subject is a patient in an Intensive Care Unit. Forcertain of these embodiments, the subject is a mechanically ventilatedpatient.

For certain embodiments of the oral care kit, including of any one ofthe above kit embodiments, the oral care kit includes at least one doseof the multi-valent cationic antiseptic composition. One dose is anamount sufficient for application to cover at least a portion of theoral tissue of a subject, preferably all of the oral mucosal tissue of asubject. For certain embodiments, one dose is 1 to 15 mL of theantiseptic composition. For certain of these embodiments, the kitincludes at least 15 mL of the multi-valent cationic antisepticcomposition. For certain of these embodiments, the kit includes at least30 mL of the multi-valent cationic antiseptic composition. For certainof these embodiments, the kit includes at least two 15 mL unit dosecontainers of the multi-valent cationic antiseptic composition. Althoughthe amounts are expressed in mL units, these amounts are understood toinclude their mass equivalents. For example, 1 mL of the multi-valentantiseptic composition is equivalent to an amount of 0.9 to 1.1 grams,depending upon the particular formulation density. In the case of thecomposition being in the form of a foam, the amount in grams may be lessthan this.

For certain embodiments, the oral care kit includes the moisturizer orsubstantive moisturizing composition supplied in an amount sufficient tocover at least a portion of the oral tissue of a subject, preferably allof the oral mucosal tissue of a subject, more preferably also includingthe lips. For certain of these embodiments, the moisturizer orsubstantive moisturizing composition is supplied in an amount sufficientfor at least one application to the oral tissue of the subject at 1 to10 grams per application. For certain of these embodiments, themoisturizer or substantive moisturizing composition is supplied in anamount sufficient for at least 4 applications to the oral tissue of thesubject at 1 to 10 grams per application. For certain of theseembodiments, the moisturizer or substantive moisturizing composition issupplied in at least 4 unit dose packages of 1 to 10 grams per package.

Significantly improved flexibility is provided by the oral care kit forapplying the moisturizer composition whenever a subject is in need of anadditional application. For example, some patients have significantlydrier mouths than others and may benefit from more frequent applicationsof the moisturizer or substantive moisturizer composition. For certainembodiments, including any one of the above oral care kit embodiments,preferably the moisturizer or substantive moisturizing composition issupplied in a single container. For certain of these embodiments, theamount of moisturizer or substantive moisturizing composition suppliedin the single container is an amount sufficient for at least 4 separateapplications to all of the oral mucosal tissue and lips of a subject.

As indicated above, the moisturizer or substantive moisturizercomposition and the multi-valent cationic antiseptic may, in certainembodiments, be applied at the same time. This may be carried out byapplying the moisturizer immediately before or after application of theantiseptic. However, for certain embodiments, including any one of theabove embodiments where the moisturizer and antiseptic are applied atthe same time, preferably the moisturizer or substantive moisturizercomposition comprises a solution of the multi-valent cationicantiseptic.

Subjects who are unable to clean their oral tissue, such as ventilatedpatients, are in need of periodic oral tissue cleaning This can becarried out using a de-briding composition, such as a hydrogen peroxidecomposition. Oral debriding refers to removal of plaque and calculusfrom the teeth but also may assist in breaking down thick mucous in theoral cavity that is otherwise difficult to remove. For certainembodiments, including any one of the above method embodiments, themethod further comprises applying a de-briding composition comprisinghydrogen peroxide. For certain embodiments, including any one of theabove oral care kit embodiments, the kit further comprises a de-bridingcomposition, which in one embodiment comprises hydrogen peroxide. Forcertain of these embodiments, the hydrogen peroxide is stabilized. Incertain embodiments, the hydrogen peroxide includes a stabilizingcomponent which maintains the de-briding composition at a pH of 2.5 to4, preferably 2.8 to 3.8, and wherein the de-briding compositionessentially excludes any component which causes a precipitate whencombined with a multi-valent cationic antiseptic used in themulti-valent cationic antiseptic composition when tested according toTest Method F. For certain of these embodiments, the hydrogen peroxideis stabilized with a buffer component selected from the group consistingof buffers such as monovalent alkyl carboxylic acids and alkylphosphoric acids wherein the alkyl group optionally comprises a carbonchain substituted with or interrupted by one or more N, O, or S atoms;polyalkoxylated derivatives such as phosphate or carboxylate terminatedpolyethoxylated and/or propoxylated alkyl alcohols; alpha-hydroxy acidssuch as lactic acid, gluconic acid, citric acid (when used at a pH whereonly one acid group is ionized); amino acids; phosphoric acid; and boricacid. Such buffer components are selected and used at concentrationssuch that a precipitate is not formed when the buffer component iscombined with the multi-valent cationic antiseptic. This can bedetermined according to Test Method F. Preferred acids have onlysubstantially a single acid group at least partially ionized at pH 3.5.For example, phosphoric acid is useful since it has pKa values of 2.15,7.2, and 12.35. Thus, at pH 3.5 there is predominantly a single ionizedgroup. Preferably, the buffer has a pKa less than 3.5, and if itcomprises a second acid functionality the second pKa is greater than 4.5as determined by standard potentiometric titration.

For certain of these embodiments, the de-briding composition is suppliedin an amount sufficient for at least one application to the oral tissueof the subject. For certain of these embodiments, the de-bridingcomposition is supplied in at least 4 unit dose containers, eachcontaining an amount sufficient for a single application to the oraltissue of the subject. For certain of these embodiments, the de-bridingcomposition is supplied in a single container in an amount sufficientfor at least 4 applications to the oral tissue of the subject.

For certain embodiments, including any one of the above method and oralcare kit embodiments which include a de-briding composition, thede-briding composition further includes a sweetener selected from thegroup consisting of sucralose, aspartame, sugars and sugar alcoholsincluding but not limited to xylose, sucrose, maltose, mannose, glucose,xylitol, sorbitol, mannitol, erythritol, maltitol, lactitol, and acombination thereof

Additional compositions may be supplied by the oral care kit. Forcertain embodiments, including any one of the above kit embodiments, theoral care kit further comprises an additional oral care compositionselected from the group consisting of an oral rinse, a toothpaste, a lipcare composition, a mouth care composition, and combinations thereof. Amouth care composition may include an analgesic, wound healing paste,tooth care composition, or other oral composition.

As indicated above, the compositions supplied by the oral care kit maybe applied with various application means. The oral care kit provides asignificant advance in flexibility of applying the above describedcomposition by supplying a plurality of applicator tools and in a mannerwhich shows compliance to a treatment protocol. Accordingly, for certainembodiments, including any one of the above kit embodiments, the oralcare kit further comprises a plurality of applicator tools for applyingat least one composition to the oral tissue of a subject. For certain ofthese embodiments, the plurality of applicator tools is selected fromthe group consisting of swabs, suction swabs, toothbrushes, suctiontoothbrushes, and combinations thereof. For certain of theseembodiments, at least a portion of the plurality of applicator tools ispackaged so that usage of the at least a portion of the plurality ofapplicator tools shows compliance with at least a portion of a protocolfor treating the oral tissue of a subject. For example, removal of atool from a particular section of the kit indicates that an applicationof a particular composition was carried out within a particular timeframe. For certain of these embodiments, the at least a portion of theplurality of applicator tools is packaged with an indication of at leastone time frame for applying at least one composition comprising the kit.For certain of these embodiments, the indication is a color code, asymbol, a picture, or a printed number.

For certain embodiments, including any one of the above embodiments ofthe kit including a plurality of applicator tools, the oral care kitcomprises a plurality of packages, wherein each package contains atleast one kit component selected from the group consisting of anapplicator tool, a suction yankaeur, a suction catheter, a Y-connector,a vacuum adapter handle, a multi-valent cationic antiseptic composition,a moisturizer or substantive moisturizing composition, a de-bridingcomposition, other mouth care products, and a combination thereof. Forcertain of these embodiments, the package is a bag, a box, a tray, or acombination thereof.

For certain embodiments, including any one of the above kit embodiments,the kit comprises a kit package comprising a plurality of pockets, eachpocket containing at least one component of the oral care kit. Referringto FIG. 1, a perspective view of one embodiment of an oral care kit 10described herein for use in treating a ventilated patient isillustrated. Oral care kit 10 includes a kit package 20 which comprisesa plurality of pockets 30. Pockets 30 may be sized the same or one ormore of the plurality of pockets may be sized differently than the otherpockets, such as illustrated by low pocket 35. Oral care kit 10 isillustrated with extension flap 40, which may include an opening orcut-out (not shown) for hanging oral care kit 10 on a hook or otherhanger means at a location convenient for use in treating a patient, forexample, near the patient's bed. Alternatively, oral care kit 10 may besimply set upon a surface, in which case flap 40 need not be used oreven present.

For certain embodiments, each pocket comprising the kit package 20 issized to accommodate at least one kit component to be held within thepocket. For example, each of pockets 30 may be sized to hold at leastone applicator tool package 60. For certain embodiments, preferably eachof pockets 30 holds a sufficient number of applicator tool packages 60so that all applications of the compositions described above and asrequired by a treatment protocol can be applied within a specified timeperiod according to the protocol using applicator tools contained withinapplicator tool packages 60 held within a particular pocket designatedfor the specified time period. For example, for certain embodiments,oral care kit 10 provides for a treatment protocol covering a specifiedtime period, and pockets 31, 32, and 33 are each designated for aseparate application time segment within the specified time period. Forcertain embodiments, oral care kit 10 provides for a 24 hour treatmentprotocol, and pockets 31, 32, and 33 are each designated for separateapplication times, for example, at 0 and 12 hours, at 4 and 16 hours,and at 8 and 20 hours, respectively. Alternative specified time periods,such as 12 hours, 36 hours, 48 hours, and the like may be used.Moreover, alternative application times may be provided, such as at 2hours, 6 hours, 10 hours, and the like. For example, pockets 31, 32, and33 may be designated for separate application times at 0, 6, 12, and 18hours; 2, 8, 14, and 20 hours; and 4, 10, 16, and 22 hours,respectively. In addition, one or more additional pockets or otherreceptacles may be included in the oral care kit to supply additionalapplicator tools for additional applications of the moisturizer orsubstantive moisturizer composition, the de-briding composition, and/orother oral care compositions as needed by the patient. Compliance with atreatment protocol can be shown or is evident by usage of applicatortools contained within applicator tool packages 60 held within each ofpockets 31, 32, and 33. For example, usage of all of the applicator toolpackages 60 in pockets 31, 32, and 33 may show compliance with a 24 hourtreatment protocol.

FIG. 1 illustrates at least one applicator tool package 60 to be heldwithin each of pockets 30. Applicator tool packages 60 each contain atleast one applicator tool. For certain embodiments, the at least oneapplicator tool is selected from the group consisting of swabs, suctionswabs, toothbrushes, suction toothbrushes, and combinations thereof. Forcertain of these embodiments, the at least one applicator tool is asuction swab. Applicator tool packages 60 may be a molded tray asillustrated in FIG. 1. However, a box, a bag, or other packaging and/orprotective means may be used. For certain embodiments, preferably atleast a portion of applicator tool packages 60 is sufficientlytransparent to allow visually viewing and identifying the contents ofapplicator tool packages 60, without opening these packages.

Low pocket 35 illustrated in FIG. 1 holds various compositions suppliedwith oral care kit 10. Moisturizer or substantive moisturizercomposition container 70 is positioned within sub-pocket 36, which inturn is contained within low pocket 35. Low pocket 35 may also holdadditional oral care composition containers, such as multi-valentcationic antiseptic composition containers, de-briding compositioncontainers, and the like. For certain embodiments, preferably low pocket35 holds at least one moisturizer or substantive moisturizer compositioncontainer 70, at least one multi-valent cationic antiseptic compositioncontainer (not shown in FIG. 1), and at least one de-briding compositioncontainer 80. For certain embodiments, all compositions held by lowpocket 35 can be visually observed simply by looking into low pocket 35.

Referring to FIG. 2, a perspective view of oral care kit 100 for use intreating a mechanically ventilated patient is illustrated. Oral care kit100 includes a kit package 120 which comprises a plurality of pockets130, as described above for pockets 30 in FIG. 1. Each of pockets 130contains two applicator tool packages 160. Applicator tool packages 160are as described above for applicator tool packages 60 in FIG. 1. Oralcare kit 100 is illustrated with extension flap 140, as described abovefor extension flap 40 in FIG. 1.

For certain embodiments, oral care kit 100 provides for a treatmentprotocol covering a specified time period, and pockets 131, 132, and 133are each designated for separate application times within the specifiedtime period. For certain embodiments, oral care kit 100 provides for a24 hour treatment protocol, and pockets 131, 132, and 133 are designatedfor separate application times, for example, 0 and 12 hours, 4 and 16hours, and 8 and 20 hours, respectively. Alternative specified timeperiods, such as 12 hours, 36 hours, 48 hours, and the like may be used.Moreover, alternative application times may be provided, as discussedabove for FIG. 1. In addition, one or more additional pockets or otherreceptacles may be included in oral care kit 100 to supply additionalapplicator tools for additional applications of the moisturizer orsubstantive moisturizer composition, the de-briding composition, and/orother oral care compositions as needed by the patient or as required bya treatment protocol. Compliance with a treatment protocol can be shownor is evident by usage of applicator tools contained within applicatortool packages 160 held within each of pockets 131, 132, and 133. Forexample, usage of all of the applicator tool packages 160 in pocket 131may show compliance with applications required by a treatment protocolat 0 and 12 hours; or usage of all of the applicator tool packages 160in pockets 131, 132, and 133 may show compliance with an entire 24 hourtreatment protocol.

Low pocket 135 illustrated in FIG. 2 holds various compositions suppliedwith oral care kit 100. Moisturizer or substantive moisturizercomposition container 170 is positioned within sub-pocket 137, which inturn is contained within low pocket 135. Low pocket 135 also holdsmulti-valent cationic antiseptic composition containers 190 withinsub-pocket 139. Low pocket 135 also holds at least one de-bridingcomposition container (not shown). Additional oral care compositions(not shown) may be held within low pocket 135 or elsewhere within oralcare kit 100, for example, in an additional pocket (not shown).

Low pocket 135 also holds auxiliary package 162 for containingadditional suction components for use in conjunction with suctionapplicator tools. For example, auxiliary package 162 may contain atleast one of a suction yankaeur, a suction catheter, a Y-connector, avacuum adapter handle, or a combination thereof. Auxiliary package 162may be a box as illustrated in FIG. 2 or alternatively may be a moldedtray, a bag, or the like, preferably a box or bag. At least a portion ofauxiliary package 162 may be sufficiently transparent to allow visualobservation of the components contained therein. In an alternativeembodiment, oral care kit 100 includes an additional pocket (not shown)for holding auxiliary package 162.

FIGS. 3 and 4 are identical to FIGS. 1 and 2, except that applicatortool packages 60 and 160, respectively, have been rotated 180 degrees.In such embodiments, the user can view any printing or other graphics onthe now exposed flat sides of applicator tool packages 60 and 160without rotating these packages.

For certain embodiments, including any one of the above method or oralcare kit embodiments which include a moisturizer composition, themoisturizer composition is preferably a substantive moisturizercomposition.

The moisturizer or substantive moisturizer composition as well ascompositions comprising the multi-valent cationic antiseptic describedabove may include at least one additional component selected from thegroup consisting of enhancers, surfactants, hydrophilic compounds,hydrophobic compounds, and combinations thereof.

Enhancer Component:

Compositions included in the present method and kit may include anenhancer to enhance the antimicrobial activity. The activity enhancementmay be especially useful against Gram negative bacteria, such as E. coliand Psuedomonas sp. The enhancer chosen preferably affects the cellenvelope of the bacteria. While not bound by theory, it is presentlybelieved that the enhancer functions by allowing the antiseptic to moreeasily enter the cell cytoplasm and/or by facilitating disruption of thecell envelope. The enhancer component may include a phenolic compound(such as certain antioxidants and parabens), a (C1-C10)monohydroxyalcohol, or a glycol ether (i.e., ether glycol). Various combinations ofenhancers can be used if desired.

In some embodiments, other enhancers may be useful, such as thesiderophores and iron-bonding proteins described in U.S. Ser. No.10/936,949, filed Sep. 8, 2004 entitled “Antimicrobial Compositions andMethods”, if they are formulated such that there is minimal or nointeraction between the multivalent cationic antiseptic and thesiderophore or iron-binding protein; and the sugar and/or alcohols asdescribed in U.S. Ser. No. 60/660,830, filed Mar. 10, 2005 entitled“Methods of Reducing Microbial Contamination.”

One or more enhancers may be used in the compositions included in thepresent method and kit at a suitable level to produce the desiredresult. For certain embodiments, they are present in a total amountgreater than 0.01 wt-%, preferably in an amount greater than 0.1 wt %,more preferably in an amount greater than 0.2 wt %, even more preferablyin an amount greater than 0.25 wt % and most preferably in an amountgreater than about 0.4 wt % based on the total weight of the ready touse composition. In a preferred embodiment, they are present in a totalamount of no greater than 20 wt-%, based on the total weight of theready to use composition. Such concentrations typically apply tophenolics, ether glycols, and (C5-C10)monohydroxy alcohols. Generally,higher concentrations are needed for (C1-C4)monohydroxy alcohols, asdescribed in greater detail below. The total concentration of theenhancer component relative to the total concentration of the antisepticcomponent is preferably within a range of 10:1 to 1:300 on a weightbasis.

An additional consideration when using an enhancer is the solubility andphysical stability in the compositions. Many of the enhancers discussedherein are insoluble in hydrophobic components such as hydrophobicesters, mineral oil, and petrolatum. It has been found that the additionof a minor amount (typically less than 30 wt-%, preferably less than 20wt-%, and more preferably less than 12 wt-%) of a hydrophilic componentnot only helps dissolve and physically stabilize the composition butimproves the antimicrobial activity as well. Alternatively, the enhancermay be present in excess of the solubility limit provided that thecomposition is physically stable. This may be achieved by utilizing asufficiently viscous composition that stratification (e.g. settling orcreaming) of the antiseptic does not appreciably occur.

A phenolic compound enhancer is typically a compound having thefollowing general structure (including at least one group bonded to thering through an oxygen:

wherein: o is 0 to 3 (especially 1 to 3), m is 1 to 3 (especially 1 to2), each R⁵ independently is alkyl or alkenyl of up to 12 carbon atoms(especially up to 8 carbon atoms) optionally substituted with 0 in or onthe chain (e.g., as a carbonyl group) or OH on the chain, and each R⁶independently is H or alkyl or alkenyl of up to 8 carbon atoms(especially up to 6 carbon atoms) optionally substituted with 0 in or onthe chain (e.g., as a carbonyl group) or OH on the chain, but where R⁶is H, o preferably is 1 or 2.

Examples of phenolic enhancers include, but are not limited to,butylated hydroxy anisole, e.g., 3(2)-tert-butyl-4-methoxyphenol (BHA),2,6-di-tert-butyl-4-methylphenol (BHT),3,5-di-tert-butyl-4-hydroxybenzylphenol, 2,6-di-tert-4-hexylphenol,2,6-di-tert-4-octylphenol, 2,6-di-tert-4-decylphenol,2,6-di-tert-butyl-4-ethylphenol, 2,6-di-tert-4-butylphenol,2,5-di-tert-butylphenol, 3,5-di-tert-butylphenol,4,6-di-tert-butyl-resorcinol, methyl paraben (4-hydroxybenzoic acidmethyl ester), ethyl paraben, propyl paraben, butyl paraben,2-phenoxyethanol, as well as combinations thereof. A preferred group ofthe phenolic derivative compounds is the phenol species having thegeneral structure shown above where R⁶=H and where R⁵ is alkyl oralkenyl of up to 8 carbon atoms, and o is 1, 2, or 3, especially whereat least one R⁵ is butyl and particularly tert-butyl, and especially thenon-toxic members thereof. Some of the preferred phenolic derivativeenhancers are BHA, BHT, methyl paraben, ethyl paraben, propyl paraben,and butyl paraben as well as combinations of these.

One or more phenolic derivative compounds may be used in thecompositions included in the present method and kit at a suitable levelto produce the desired result. The concentrations of the phenoliccompounds in medical-grade compositions may vary widely, but as littleas 0.001 wt-%, based on the total weight of the composition, can beeffective when the above-described esters are present within theabove-noted ranges. In certain embodiments, they are present in a totalamount of at least 0.01 wt-%, more preferably at least 0.10 wt-%, andeven more preferably at least 0.25 wt-%, based on the ready to usecomposition. In a preferred embodiment, they are present in a totalamount of no greater than 8 wt-%, more preferably no greater than 4wt-%, and even more preferably no greater than 2 wt-%, based on theready to use composition. It is preferred that the ratio of the totalphenolic concentration to the total concentration of the antisepticcomponent be within a range of 10:1 to 1:300 on a weight basis.

The above-noted concentrations of the phenolic derivative enhancers arenormally observed unless concentrated formulations for subsequentdilution are intended. On the other hand, the minimum concentration ofthe phenolics and the antiseptic to provide an antimicrobial effect willvary with the particular application.

(C1-C10) Monohydroxy alcohol enhancers include the lower (i.e., C1-C4)monohydroxy alcohols (e.g., methanol, ethanol, isopropanol, and butanol)as well as longer chain (i.e., C5-C10) monohydroxy alcohols (e.g.,isobutanol, t-butanol, octanol, and decanol). In certain preferredembodiments, the alcohols useful in the compositions included in thepresent method and kit are selected from the group consisting ofmethanol, ethanol, isopropyl alcohol, and mixtures thereof.

One or more alcohols may be used in the compositions included in thepresent method and kit at a suitable level to produce the desiredresult. In one embodiment, the short chain (i.e., C1-C4) alcohols arepresent in a total amount of at least 5 wt-%, even more preferably atleast 10 wt-%, even more preferably at least 15 wt-%, and even morepreferably at least 20 wt-%, based on the total weight of the ready touse composition. In a preferred embodiment, the (C1-C4)alcohols arepresent in a total amount of no greater than 50 wt-%, more preferably nogreater than 40 wt-%, and even more preferably no greater than 30 wt-%,based on the total weight of the ready to use composition.

For certain applications, lower alcohols may not be preferred due to thestrong odor and potential for stinging and irritation. This can occurespecially at higher levels. In applications where stinging or burningis a concern, the concentration of (C1-C4)alcohols is preferably lessthan 20%, more preferably less than about 15%.

In certain embodiments, longer chain (i.e., C5-C10) alcohols are presentin a total amount of at least 0.1 wt-%, more preferably at least 0.25wt-%, and even more preferably at least 0.5 wt-%, and most preferably atleast 1.0%, based on the ready to use composition. In a preferredembodiment, the (C5-C10)alcohols are present in a total amount of nogreater than 10 wt-%, more preferably no greater than 5 wt-%, and evenmore preferably no greater than 2 wt-%, based on the total weight of theready to use composition.

Ether glycol enhancers include those of the formula:R′—O—(CH₂CHR″O)_(p)(CH₂CHR″O)Hwherein R′=H, a (C1-C8)alkyl, a (C6-C12) aryl or a (C6-C12)aralkyl or(C6-C12) alkaryl; and each R″ is independently=H, methyl, or ethyl; andp=0-5, preferably 1-3. Examples include 2-phenoxyethanol, dipropyleneglycol, triethylene glycol, the line of products available under thetrade designation DOWANOL DB (di(ethylene glycol) butyl ether), DOWANOLDPM (di(propylene glycol)monomethyl ether), and DOWANOL TPnB(tri(propylene glycol) monobutyl ether), as well as many othersavailable from Dow Chemical, Midland Mich. Some of these compounds arenot suitable for use in the oral environment but may be useful on othermucosal tissues.

One or more ether glycols may be used in the compositions included inthe present method and kit at a suitable level to produce the desiredresult. In a preferred embodiment, they are present in a total amount ofat least 0.01 wt-%, based on the total weight of the ready to usecomposition. In a preferred embodiment, they are present in a totalamount of no greater than 20 wt-%, based on the total weight of theready to use composition.

Surfactants:

Compositions included in the present method and kit may include one ormore surfactants to emulsify the composition and to help the compositionwet the surface and/or to aid in contacting the microorganisms. As usedherein the term “surfactant” means an amphiphile (a molecule possessingboth polar and nonpolar regions which are covalently bound) capable ofreducing the surface tension of water and/or the interfacial tensionbetween water and an immiscible liquid. The surfactant can be cationic,nonionic, or amphoteric. Combinations of surfactants can be used ifdesired.

In certain embodiments, preferably the surfactants useful in thecompositions included in the present method and kit are selected fromthe group consisting of certain poloxamer (polyethyleneoxide/polypropylene oxide block copolymers) surfactants, cationicsurfactants, zwitterionic surfactants, and mixtures thereof. Cationic,amphoteric, and non-ionic surfactants and in particular certain ethyleneoxide/propylene oxide surfactants such as poloxamers are preferred.

One or more surfactants may be used in the compositions included in thepresent method and kit at a suitable level to produce the desiredresult. In certain embodiments, they are present in a total amount of atleast 0.01 wt-%, preferably 0.1 wt %, more preferably at least 0.5 wt-%,and even more preferably at least 1.0 wt-%, based on the total weight ofthe ready to use composition. In certain embodiments where, for example,irritation may be a concern, they are present in a total amount of nogreater than 10 wt-%, more preferably no greater than 5 wt-%, and evenmore preferably no greater than 2 wt-%, based on the total weight of theready to use composition. The ratio of the total concentration ofsurfactant to the total concentration of the antiseptic is preferablywithin a range of 5:1 to 1:100.

Exemplary cationic surfactants include, but are not limited to, salts ofoptionally polyoxyalkylenated primary, secondary, or tertiary fattyamines; quaternary ammonium salts such as tetraalkylammonium,alkylamidoalkyltrialkylammonium, trialkylbenzylammonium,trialkylhydroxyalkylammonium, or alkylpyridinium having compatibleanionic counterions such as halides (preferably chlorides or bromides)or alkyl sulfates such as methosulfate or ethosulfate as well as otheranionic counterions; imidazoline derivatives; amine oxides of a cationicnature (e.g., at an acidic pH), and mixtures thereof.

In certain preferred embodiments, the cationic surfactants useful in thepresent methods and kits are selected from the group consisting oftetralkyl ammonium, trialkylbenzylammonium, and alkylpyridinium halides,and mixtures thereof.

Also particularly preferred are amine oxide surfactants including alkyland alkylamidoalkyldialkylamine oxides of the following formula:(R¹⁴)₃—N→Owherein R¹⁴ is a (C1-C30)alkyl group (preferably a (C1-C14)alkyl group)or a (C6-C18)aralkyl or alkaryl group, wherein any of these groups canbe optionally substituted in or on the chain by N-, O-, or S-containinggroups such as amide, ester, hydroxyl, and the like. Each R¹⁴ may be thesame or different provided at least one R¹⁴ group includes at leasteight carbons. Optionally, the R¹⁴ groups can be joined to form aheterocyclic ring with the nitrogen to form surfactants such as amineoxides of alkyl morpholine, alkyl piperazine, and the like. Preferablytwo R¹⁴ groups are methyl and one R¹⁴ group is a (C12-C16)alkyl oralkylamidopropyl group. Examples of amine oxide surfactants includethose commercially available under the trade designations AMMONYX LO,LMDO, and CO, which are lauryldimethylamine oxide,laurylamidopropyldimethylamine oxide, and cetyl amine oxide, all fromStepan Company of Northfield, Ill.

Amphoteric surfactants include those having tertiary amine groups, whichmay be protonated, as well as quaternary amine containing zwitterionicsurfactants. Examples include:

Ammonium carboxylate amphoterics, which can be represented by thefollowing formula:R¹⁷—(C(O)—NH)_(a)—R¹⁸—N⁺(R¹⁹)₂—R²⁰—COO⁻wherein: a=0 or 1; R¹⁷ is a (C7-C21)alkyl group (saturated straight,branched, or cyclic group), a (C6-C22)aryl group, or a (C6-C22)aralkylor alkaryl group (saturated straight, branched, or cyclic alkyl group),wherein R¹⁷ may be optionally substituted with one or more N, O, or Satoms, or one or more hydroxyl, carboxyl, amide, or amine groups; R¹⁹ isH or a (C1-C8)alkyl group (saturated straight, branched, or cyclicgroup), wherein R¹⁹ may be optionally substituted with one or more N, O,or S atoms, or one or more hydroxyl, carboxyl, amine groups, a(C6-C9)aryl group, or a (C6-C9)aralkyl or alkaryl group; and R¹⁸ and R²⁰are each independently a (C1-C10)alkylene group that may be the same ordifferent and may be optionally substituted with one or more N, O, or Satoms, or one or more hydroxyl or amine groups.

More preferably, in the formula above, R¹⁷ is a (C1-C18)alkyl group, R¹⁹is a (C1-C2)alkyl group preferably substituted with a methyl or benzylgroup and most preferably with a methyl group. When R¹⁹ is H it isunderstood that the surfactant at higher pH values could exist as atertiary amine with a cationic counterion such as Na, K, Li, or aquaternary amine group.

Examples of such amphoteric surfactants include, but are not limited to:certain betaines such as cocobetaine and cocamidopropyl betaine(commercially available under the trade designations MACKAM CB-35 andMACKAM L from McIntyre Group Ltd., University Park, Ill.); monoacetatessuch as sodium lauroamphoacetate; diacetates such as disodiumlauroamphoacetate; amino- and alkylamino-propionates such aslauraminopropionic acid (commercially available under the tradedesignations MACKAM 1L, MACKAM 2L, and MACKAM 151L, respectively, fromMcIntyre Group Ltd.).

Ammonium sulfonate amphoteric surfactants are often referred to as“sultaines” or “sulfobetaines” and can be represented by the followingformulaR¹⁷—(C(O)—NH)_(n)—R¹⁸—N⁺(R¹⁹)₂—R²⁰SO₃ ⁻wherein R¹⁷-R²⁰ and “a” are defined above. Examples includecocamidopropylhydroxysultaine (commercially available as MACKAM 50-SBfrom McIntyre Group Ltd.). The sulfoamphoterics may be preferred overthe carboxylate amphoterics since the sulfonate group will remainionized at much lower pH values.

Exemplary nonionic surfactants include, but are not limited to, alkylglucosides, alkyl polyglucosides, polyhydroxy fatty acid amides, sucroseesters, esters of fatty acids and polyhydric alcohols, fatty acidalkanolamides, ethoxylated fatty acids, ethoxylated aliphatic acids,ethoxylated fatty alcohols (e.g., octyl phenoxy polyethoxyethanolavailable under the trade name TRITON X-100 and nonyl phenoxypoly(ethyleneoxy) ethanol available under the trade name NONIDET P-40,both from Sigma, St. Louis, Mo.), ethoxylated and/or propoxylatedaliphatic alcohols (e.g., that available under the trade name Brij fromICI), ethoxylated glycerides, ethoxylated/propoxylated block copolymerssuch as the Pluronic and Tetronic surfactants available from BASF,ethoxylated cyclic ether adducts, ethoxylated amide and imidazolineadducts, ethoxylated amine adducts, ethoxylated mercaptan adducts,ethoxylated condensates with alkyl phenols, ethoxylated nitrogen-basedhydrophobes, ethoxylated polyoxypropylenes, polymeric silicones,fluorinated surfactants (e.g., those available under the trade namesFLUORAD-FS 300 from 3M Company, St. Paul, Minn., and ZONYL from Dupontde Nemours Co., Wilmington, Del.), and polymerizable (reactive)surfactants (e.g., SAM 211 (alkylene polyalkoxy sulfate) surfactantavailable under the trade name MAZON from PPG Industries, Inc.,Pittsburgh, Pa.). In certain preferred embodiments, the nonionicsurfactants useful in the compositions of the present invention areselected from the group consisting of Poloxamers such as PLURONIC fromBASF, sorbitan fatty acid esters, and mixtures thereof.

Hydrophilic Component:

Compositions of the present methods and kits can include a hydrophilicor water-soluble component to help solubilize and/or physicallystabilize the antiseptic and/or enhancer component in the compositionand/or to enhance the antimicrobial efficacy and/or the speed ofantimicrobial efficacy. The incorporation of a sufficient amount ofhydrophilic component in hydrophobic ointments for use in applicationssuch as lip care compositions results in compositions with significantlybetter antimicrobial activity both in terms of speed of kill and extentof kill. While not intended to be bound by theory it is believed thatthe incorporation of the hydrophilic component allows more antiseptic tobe available at the surface or to more rapidly diffuse to the surface ofthe ointment during use. Certain compositions may be solutions,emulsions (one liquid/gel/paste dispersed in another liquid/gel/paste),or dispersions (solid in liquid/paste/gel). In general, for improvedantimicrobial activity the ratio of total hydrophilic component to totalhydrophobic component (water insoluble ingredients) should be at least5:95 wt/wt, preferably at least 10:90 wt/wt, more preferably at least15:85 wt/wt and most preferably at least 20:80 wt/wt. Levels as high as30:70, 40:60, 50:50 wt/wt of total hydrophilic component to totalhydrophobic component (water insoluble ingredients) or higher may beappropriate for certain compositions.

A hydrophilic material is typically a compound that has a solubility inwater of at least 7 wt-%, preferably at least 10 wt-%, more preferablyat least 20 wt-%, even more preferably at least 25 wt-%, and even morepreferably at least 40 wt-%, at 23° C. Most preferably, a hydrophiliccomponent is infinitely miscible with water at 23° C.

Exemplary hydrophilic components include, but are not limited to, water,polyhydric alcohols, lower alkyl ethers (i.e., having a sufficientlysmall number of carbon atoms to meet the solubility limit above),N-methylpyrrolidone, alkyl esters (i.e., having a sufficiently smallnumber of carbon atoms to meet the solubility limit above), and thelower monohydroxy alcohols discussed above as enhancers, as well ascombinations thereof. Thus, a lower monohydroxy alcohol can function asboth a hydrophilic compound and an enhancer. Preferably, the hydrophiliccomponents include polyhydric alcohols, lower alkyl ethers, and shortchain esters. More preferably, the hydrophilic components includepolyhydric alcohols.

Suitable polyhydric alcohols (i.e., organic compounds having more thanone hydroxyl group) have a molecular weight of less than 500, preferablyless than 400, and more preferably less than 200. Examples of polyhydricalcohols include, but are not limited to, glycerol, propylene glycol,dipropylene glycol, tripropylene glycol, polypropylene glycol,polyethylene glycol, diethylene glycol, pentaerythritol,trimethylolpropane, trimethylolethane, trimethylolbutane, sorbitol,mannitol, xylitol, pantothenol, ethylene glycol adducts of polyhydricalcohol, propylene oxide adducts of polyhydric alcohol, 1,3-butanediol,dipropylene glycol, diglycerine, polyglycerine, erythritol, sorbitan,sugars (e.g., sucrose, glucose, fructose, mannose, xylose, saccharose,trehalose), sugar alcohols, and the like. Certain preferred polyhydricalcohols include glycols (i.e., those containing two hydroxyl groups)including glycerin and propylene glycol. Certain other preferredpolyhydric alcohols include xylitol, mannitol, sorbitol, sucrose andpolyglycerin.

Ethers include materials such as dimethylisosorbide, polyethylene glycoland methoxypolyethylene glycols, block and random copolymers of ethyleneoxide and propylene oxide, and laureth-4. Alkyl esters includetriacetin, methyl acetate, esters of polyethoxylated glycols, andcombinations thereof.

In certain preferred embodiments, the hydrophilic components useful inthe compositions of the present invention include those selected fromthe group consisting of glycols, and in particular glycerin, xylitol,and propylene glycol, and mixtures thereof.

If there are components in the composition that may esterify withhydroxylfunctional hydrophilic components conditions are selected tominimize this occurrence. For example, the components are not heatedtogether for extended periods of time, the pH is maintained close toneutral if possible, and the like.

One or more hydrophilic materials may be used in the compositions of thepresent methods and kits at a suitable level to produce the desiredresult. In certain embodiments that also include a hydrophobic componentas the component used in the greatest amount (which may be referred toas a “vehicle”), the hydrophilic component is present in a total amountof at least 0.1%, preferably at least 1 wt-%, more preferably at least 4wt-%, and even more preferably at least 8 wt-%, based on the weight ofthe ready to use composition In certain embodiments, the hydrophiliccomponent is present in a total amount of at least 10% by weight, atleast 20% by weight, or at least 25% by weight. In certain embodiments,the hydrophilic component is present in a total amount of no greaterthan 70 wt-%, no greater than 60 wt-%, or no greater than 50 wt-%, basedon the ready to use composition. When the hydrophilic component ispresent in the greatest amount it is referred to as a “vehicle.”

For certain applications it may be desirable to formulate theseantiseptics in compositions comprising a hydrophilic component vehiclethat is thickened with soluble, swellable or insoluble (e.g. insoluble)organic polymeric thickeners or inorganic thickeners such as silica,fumed silica, precipitated silica, silica aerogel, and the like; otherparticle fillers such as calcium carbonate, magnesium carbonate, kaolin,talc, titanium dioxide, aluminum silicate, diatomaceous earth, ferricoxide and zinc oxide, clays, and the like; ceramic microspheres or glassmicrobubbles; ceramic microspheres such as those available under thetradenames “ZEOSPHERES” or “Z-LIGHT” from 3M. The above fillers can beused alone or in combination. Preferably, inorganic thickeners arecompatible with the multi-valent cationic antiseptic. For certainembodiments, preferably the inorganic thickeners are very insoluble.

For certain embodiments, water can be used in significant amounts (e.g.,at least 20 wt-%), and can even be the primary component, as long as thecomposition is highly viscous. Preferably, such highly viscouscompositions have a viscosity of at least 20 cps, preferably, 50centipoise (cps), more preferably at least 100 cps, even more preferablyat least 1000 cps, even more preferably at least 2000 cps, even morepreferably at least 5000 cps, even more preferably at least 7500 cps,even more preferably at least 10,000 cps, at least 25,000 cps, or ashigh as about 50,000 cps or 1,000,000 cps, or more. The viscosity can bemeasured as described below in the Viscosity Test. Most preferredcompositions meet these viscosity values even after heating to 32 C.° oreven 35 C.° or as high as 37 C.° to ensure when in contact withmammalian tissue the compositions remain substantive.

Hydrophobic Component:

Certain preferred compositions of the present methods and kits alsoinclude one or more hydrophobic materials. A hydrophobic material istypically an organic compound, which at 23° C. is a liquid, gelatinous,semisolid or solid and has a solubility in water of less than 5% byweight, preferably less than 1% by weight, more preferably less than0.5% by weight, and even more preferably less than 0.1% by weight. Thesematerials include compounds typically considered emollients in thecosmetic art.

Examples of general emollients include, but are not limited to, C6-C22alkyl mono, di and tri esters of glycerin and propylene glycol,vegetable oils, short chain (i.e, C1-C6) alkyl or (C6-C12)aryl esters oflong (i.e., C8-C36) straight or branched chain alkyl or alkenyl alcoholsor acids and polyethoxylated derivatives of the alcohols; short chain(i.e., C1-C6) alkyl or (C6-C12)aryl esters of (C4-C12)diacids or(C4-C12)diols optionally substituted in available positions by —OH;(C2-C18)alkyl or (C6-C12)aryl esters of glycerol, pentaerythritol,ethylene glycol, propylene glycol, as well as polyethoxylatedderivatives of these; (C12-C22)alkyl esters or (C12-C22)ethers ofpolypropylene glycol; (C12-C22)alkyl esters or (C12-C22)ethers ofpolypropylene glycol/polyethylene glycol copolymer; and polyetherpolysiloxane copolymers. Additional examples of hydrophobic componentsinclude cyclic dimethicones including volatile cyclic silicones such asD3 and D4, polydialkylsiloxanes, polyaryl/alkylsiloxanes, siliconecopolyols, long chain (i.e., C8-C36) alkyl and alkenyl esters of long(i.e., C8-C18) straight or branched chain alkyl or alkenyl alcohols oracids, long chain (i.e., C8-C36) alkyl and alkenyl amides of longstraight or branched chain (i.e., C8-C36) alkyl or alkenyl amines oracids; hydrocarbons including straight and branched chain alkanes andalkenes such as isoparafins (e.g. isooctane, isododecane, isooctadecane,etc.), squalene, and mineral oil, polysiloxane polyalkylene copolymers,dialkoxy dimethyl polysiloxanes; (C12-C22)alkyl and (C12-C22)alkenylalcohols, and petroleum derived alkanes such as isoparafins, petrolatum,petrolatum USP, as well as refined natural oils (especially NF or USPgrades) such as olive oil NF, cotton seed oil, peanut oil, corn oil,seasame oil, safflower oil, soybean oil, and the like, and blendsthereof.

In certain preferred embodiments, the hydrophobic components useful inthe compositions of the present methods and kits include those selectedfrom the group consisting of vegetable oils, C6-C22 alkyl mono, di andtri esters of glycerin and propylene glycol, petrolatum USP and shortchain (i.e., C1-C6) alkyl or (C6-C12)aryl esters of long (i.e., C8-C36)straight or branched chain alkyl or alkenyl alcohols or acids andpolyethoxylated derivatives of the alcohols; short chain (i.e., C1-C6)alkyl or (C6-C12)aryl esters of (C4-C12)diacids or (C4-C12)diolsoptionally substituted in available positions by —OH (such asdiisopropyladipate, diisopropylsebacate); (C1-C9)alkyl or (C6-C12)arylesters of glycerol, pentaerythritol, ethylene glycol, propylene glycol(such as glyceryl tricaprylate/caprate); and mixtures thereof. Forcertain embodiments, preferably the hydrophobic component is selectedfrom one or more vegetable oils, C6-C22 alkyl mono, di and tri esters ofglycerin and propylene glycol, and combinations thereof.

One or more hydrophobic materials may be used in the compositions of thepresent methods and kits at a suitable level to produce the desiredresult. In certain embodiments, the hydrophobic component is present ina total amount of at least 30 wt-%, preferably at least 50 wt-%, morepreferably at least 60 wt-%, and even more preferably at least 70 wt-%,based on the ready to use composition. In certain of these embodiments,the hydrophobic component is present in a total amount of no greaterthan 99 wt-%, more preferably no greater than 95 wt-%, and even morepreferably no greater than 92 wt-%, based on the ready to usecomposition. When the hydrophobic component is present in the greatestamount it is referred to as a “vehicle.” If the hydrophobic component(s)and the hydrophilic component(s) are present at the same concentrationsthe continuous phase is consider the “vehicle”. In other embodimentssuch as hydrophilic solutions and gels as well as emulsions, thecomposition may be for general use in the oral cavity. Where aspirationof the composition into the lung is concerned such as treatment ofpatients on mechanical ventilation it may be desirable to limit theamount of hydrophobic component in order to prevent lipoid pneumonia. Inthese applications the hydrophobic component may be present at less than10 percent by weight of the composition or less than 5 percent or lessthan 3 percent or even less than 2 percent by weight of the composition.In certain embodiments the oral care composition may be essentially freeof water insoluble or hydrophobic components.

Optional Additives:

Compositions of the present methods and kits may additionally employadjunct components conventionally found in pharmaceutical compositionsin their art-established fashion and at their art-established levels.Thus, for example, the compositions may contain additional compatiblepharmaceutically active materials for combination therapy (such assupplementary antimicrobials, anti-parasitic agents, antipruritics,astringents, local anaesthetics, steroids, non-steorodialantinflammatory agents, or other anti-inflammatory agents), antiplaque,antigingivitis, or may contain materials useful in physicallyformulating various dosage forms of the present invention, such asexcipients, flavors, vitamins, dyes, perfumes, fragrances, lubricants,thickening agents, stabilizers, tissue penetration enhancers,preservatives, or antioxidants.

It will be appreciated by the skilled artisan that the levels or rangesselected for the required or optional components described herein willdepend upon whether one is formulating a composition for direct use, ora concentrate for dilution prior to use, as well as the specificcomponent selected, the ultimate end-use of the composition, and otherfactors well known to the skilled artisan.

In those applications where emulsions are desirable, an emulsifier maybe used. As used herein, an “emulsifier” means a small molecule orpolymeric amphiphilic compound capable of helping to stabilize anemulsion when used alone or in combination with other emulsifiers orcomponents. Emulsifiers used herein include many of the surfactantsdisclosed but may also include many other amphiphilic molecules. Theemulsions are detectably more stable with the emulsifier present thanwithout as determined by centrifugation and/or freeze thaw studies.

It will also be appreciated that additional antiseptics, disinfectants,or antibiotics may be included and are contemplated. These include, forexample, addition of metals such as silver, copper, zinc; iodine andiodophors: “azole” antifungal agents including clortrimazole,miconazole, econazole, ketoconazole, metronizazole, and salts thereof;and the like. Antibiotics such as tobramycin, clindamycin, tetracycline,neomycin sulfate, bacitracin, mupirocin, tetracycline, polymixin, andthe like, also may be included. Preferred compositions, however, arefree of antibiotics due to the chance of resistance formation.

As indicated above there is also provided herein a method ofmoisturizing oral tissue of a patient requiring intubation, wherein acationic antiseptic compatible moisturizer composition is used inconjunction with an endotracheal tube, which is coated or impregnatedwith the cationic antiseptic. Further, in another embodiment, there isprovided a kit comprising a moisturizer composition for application tooral tissue, to an endotracheal tube, or both the oral tissue and theendotracheal tube; and at least one endotracheal tube; wherein theendotracheal tube is coated or impregnated with a cationic antiseptic;wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the cationic antisepticwhen tested according to Test Method F; and wherein the cationicantiseptic is other than a metal ion. Here the moisturizer compositioncan be any one of the moisturizer compositions described herein, and canbe applied as described herein for any of these compositions. Applyingthe moisturizer composition can be carried out before, during, or afterinserting the endotracheal tube. The moisturizer composition not onlyprovides a moisturizing effect to the patients oral tissue, but can alsoact as a lubricant to ease insertion of the endotracheal tube. Themoisturizer composition can be applied to the patient's oral tissue, tothe surfaces of the endotracheal tube, or to both the oral tissue andthe endotracheal tube without causing a significant reduction in theantimicrobial activity of the cationic antiseptic associated with theendotracheal tube as a result of contact with between the moisturizercomposition and the endotracheal tube.

Endotracheal tubes which can be used in the above method include thosedescribed in U.S. Patent Application No. 2009/0032027. Usefulendotracheal tube materials includes polyurethane (PU), low-densitypolyethylene (LDPE), metallocene polyolefins such as metallocenepolyethylene and polypropylene, silicones such as silicones cured bymoisture or hydrosilation, polyvinyl chloride (PVC), polyamid (PA) orpolyesters including elastomeric polyesters such as Hytrel brandpolyesters, as well as fluoropolymers such as Teflon andfluoroelastomers as well as blends, mixtures, and laminates orcoextrusions thereof, and combinations thereof.

Coated endotracheal tubes can be prepared by applying a cationicantiseptic composition to an endotracheal tube using coating methodssuch as dip coating, extrusion coating, vapor deposition, spraying, andthe like as well as combinations thereof. The cationic antisepticcomposition for coating the endotracheal tube includes at least onecationic antiseptic as described herein, an optional suitable carrierfor dissolving or dispersing the antiseptic, and optionally a filmforming polymer. Suitable cationic antiseptics include the multi-valentcationic antiseptics described above, as well as other cationicantiseptics described in U.S. Patent Application No. 2006/211533,including, for example, small molecule quaternary ammonium compoundssuch as benzalkoium chloride and alkyl substituted derivatives; di-longchain alkyl (C8-C18) quaternary ammonium compounds; cetylpyridiniumhalides and their derivatives; benzethonium chloride and its alkylsubstituted derivatives; octenidine and combinations thereof.

Preferred carriers do not dissolve or compromise the physical strengthand structural integrity of the endotracheal tube. The carrier mayattack the substrate temporarily during coating in order to promoteadequate bonding of the coating. Suitable carriers include, for example,solvents such as volatile esters, ketones, alkanes, ethers, toluene,xylene as well as water, and combinations thereof.

Optional film forming polymers include polyurethanes, polyvinylchloride,polyacrylates, silicones, fluoropolymers, polyolefins, polyamides,polyethers, copolymers such as ethylene vinylacetate, polymers made fromethylenically unsaturated monomers and combinations thereof. The filmforming polymer may be linear, branched, hyperbranched, or crosslinked.See, for example, U.S. Pat. No. 6,949,958.

Endotracheal tubes impregnated with the a multi-valent cationicantiseptic can be prepared by extrusion or curing such as dip coatingand subsequently initiating cure.

LISTING OF EMBODIMENTS

The following is a listing of certain of the embodiments describedherein:

-   1. A method of moisturizing while decolonizing mammalian tissue, the    method comprising:

applying a multi-valent cationic antiseptic composition to oral tissue,and

applying a moisturizer composition to at least a portion of the oraltissue;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with a multi-valent cationicantiseptic used in the multi-valent cationic antiseptic composition whentested according to Test Method F;

wherein the multi-valent cationic antiseptic is other than a metal ion.

-   2. The method of embodiment 1, wherein the essentially excluded    component is selected from the group consisting of polyanions of    polycarboxylates, polysulfonates, polysulfates, and organic and    inorganic polyphosphates; anions of alkylsulfates, arylsulfates,    alkylsulfonates, arylsulfonates, alkylcarboxylates,    arylcarboxylates, alkylphosphates, arylphosphates; halide salts; and    combinations thereof, wherein the alkyl groups have a chain length    of greater than 6 carbon atoms and the aryl groups have 6 or more    carbon atoms, and wherein the essentially excluded component is not    present or present at a concentration less than 0.1 percent by    weight of the composition, except halide salts which are not present    or present at a concentration not greater than 0.2 wt-% by weight of    the composition.-   3. The method of embodiment 1 or embodiment 2, wherein the    moisturizer composition is such that a log reduction in the number    of viable bacterial cells of at least 2 is provided when 10⁶ cfu of    Pseudomonas aeruginosa (ATCC 27853) are combined with a mixture of    1.1 g of the moisturizer composition and 1.5 g of a multi-valent    cationic antiseptic composition containing 0.12 weight percent of    the multi-valent cationic antiseptic according to Test Method B.-   4. A method of moisturizing while decolonizing mammalian tissue, the    method comprising:

applying a multi-valent cationic antiseptic to the tissue, and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein the substantive moisturizer composition is such that a logreduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853) arecombined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B.

-   5. The method of embodiment 3 or embodiment 4, wherein the    moisturizer composition is such that a log reduction in the number    of viable bacterial cells of at least 3 is provided.-   6. The method of embodiment 4 or embodiment 5, wherein the    substantive moisturizer composition essentially excludes a component    selected from the group consisting of polyanions of    polycarboxylates, polysulfonates, polysulfates, and polyphosphates;    chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,    alkylsulfonates, arylsulfonates, alkylcarboxylates,    arylcarboxylates, alkylphosphates, arylphosphates; and combinations    thereof; wherein the alkyl groups have a chain length of greater    than four carbon atoms, and the aryl groups include at least 6    carbon atoms.-   7. The method of any one of embodiments 1 through 6, wherein the    moisturizer composition has a pH of 3 to 8.-   8. The method of any one of embodiments 1 through 7, wherein the    moisturizer composition has a viscosity of at least 50 centipoise.-   9. The method of any one of embodiments 1 through 8, wherein the    multi-valent cationic antiseptic is selected from the group    consisting of biguanides, bisbiguanides, polybiguanides, polymeric    quaternary ammonium compounds, and combinations thereof.-   10. The method of embodiment 9, wherein the multi-valent cationic    antiseptic is a chlorhexidine salt.-   11. The method of any one of embodiments 1 through 10, wherein the    multi-valent cationic antiseptic is included in a composition    comprising a solution of the multi-valent cationic antiseptic at    0.05 to 0.4 weight percent.-   12. The method of any one of embodiments 1 through 11, wherein the    multi-valent cationic antiseptic is included in a composition    further comprising a sweetener selected from the group consisting of    sucralose, aspartame, xylose, sucrose, maltose, mannose, glucose,    xylitol, sorbitol, mannitol, erythritol, maltitol, lactitol, and a    combination thereof.-   13. The method of any one of embodiments 1 through 12, wherein the    substantive moisturizer composition is applied after applying the    cationic antiseptic.-   14. The method of any one of embodiments 1 through 12, wherein the    substantive moisturizer composition is applied before applying the    cationic antiseptic.-   15. The method of any one of embodiments 1 through 14, wherein the    moisturizer composition and the multi-valent cationic antiseptic are    applied within 12 hours of each other.-   16. The method of any one of embodiments 13, 14, and 15, wherein the    substantive moisturizer composition and the multi-valent cationic    antiseptic are applied within 4 hours of each other.-   17. The method of any one of embodiments 13 through 16, wherein the    substantive moisturizer composition and the multi-valent cationic    antiseptic are applied within less than 30 minutes of each other.-   18. The method of any one of embodiments 1 through 12, wherein the    moisturizer composition is applied at the same time as applying the    multi-valent cationic antiseptic.-   19. The method of any one of embodiments 1 through 18, wherein the    moisturizer composition is applied in an amount of 1 to 10 grams per    application.-   20. The method of any one of embodiments 1 through 19, wherein the    moisturizer composition has a shrinkage of less than 10 percent when    dried under ambient conditions for 2 hours.-   21. The method of any one of embodiments 1 through 20, wherein the    substantive moisturizer composition when dried on a surface under    ambient conditions cannot be peeled from the surface in a single    piece.-   22. The method of any one of embodiments 1 through 21, wherein the    moisturizer composition when dried on a surface under ambient    conditions does not form a self supporting film.-   23. The method of any one of embodiments 1 through 22, further    comprising applying a de-briding composition comprising hydrogen    peroxide.-   24. The method of embodiment 23, wherein the hydrogen peroxide is    stabilized with a component which maintains the de-briding    composition at a pH of 2.5 to 4, and wherein the de-briding    composition essentially excludes any component which causes a    precipitate when combined with a multi-valent cationic antiseptic    used in the multi-valent cationic antiseptic composition when tested    according to Test Method F.-   25. The method of embodiment 24, wherein the hydrogen peroxide is    stabilized with a buffer component selected from the group    consisting of monovalent alkyl carboxylic acids and alkyl phosphoric    acids wherein the alkyl group optionally comprises a carbon chain    substituted with or interrupted by one or more N, O, or S atoms;    phosphate or carboxylate terminated polyethoxylated and/or    propoxylated alkyl alcohols; alpha-hydroxy acids; amino acids;    phosphoric acid; and boric acid; wherein the buffer component is    selected and used at concentrations such that a precipitate is not    formed when the buffer component is combined with the multi-valent    cationic antiseptic.-   26. The method of any one of embodiments 1 through 25, wherein the    oral tissue is oral mucosal tissue.-   27. The method of embodiment 26, wherein the oral mucosal tissue is    selected from the group consisting gingiva, buccal mucosa, the floor    of the mouth, the hard palate, the soft palate, the dorsal tongue,    the lateral tongue, the ventral tongue, an oropharyngeal surface,    and combinations thereof.-   28. The method of any one of embodiments 1 through 27, wherein the    subject is a patient in an Intensive Care Unit.-   29. The method of any one of embodiments 1 through 28, wherein the    subject is a mechanically ventilated patient.-   30. An oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a moisturizer composition;

wherein each composition is for application to oral tissue of a subject;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the multi-valent cationicantiseptic when tested according to Test Method F;

wherein the multi-valent cationic antiseptic is other than a metal ion.

-   31. The oral care kit of embodiment 30, wherein the essentially    excluded component is selected from the group consisting of    polyanions of polycarboxylates, polysulfonates, polysulfates, and    organic and inorganic polyphosphates; anions of alkylsulfates,    arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,    arylcarboxylates, alkylphosphates, arylphosphates; halide salts; and    combinations thereof, wherein the alkyl groups have a chain length    of greater than 6 carbon atoms and the aryl groups have 6 or more    carbon atoms, and wherein the essentially excluded component is not    present or present at a concentration less than 0.1 percent by    weight of the composition, except halide salts which are not present    or present at a concentration not greater than 0.2 wt-% by weight of    the composition.-   32. The oral care kit of embodiment 30 or embodiment 31, wherein the    moisturizer composition is such that a log reduction in the number    of viable bacterial cells of at least 2 is provided when 10⁶ cfu of    Pseudomonas aeruginosa (ATCC 27853) are combined with a mixture of    1.1 g of the substantive moisturizer composition and 1.5 g of a    multi-valent cationic antiseptic composition containing 0.12 weight    percent of the multi-valent cationic antiseptic according to Test    Method B.-   33. An oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein the substantive moisturizer composition is such that a logreduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853) arecombined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of the multi-valent cationic antisepticcomposition containing 0.12 weight percent of the multi-valent cationicantiseptic according to Test Method B.

-   34. The oral care kit of embodiment 33, wherein the substantive    moisturizer composition is such that a log reduction in the number    of viable bacterial cells of at least 3 is provided.-   35. The oral care kit of embodiment 33 of embodiment 34, wherein the    substantive moisturizer composition essentially excludes a component    selected from the group consisting of polyanions of    polycarboxylates, polysulfonates, polysulfates, and polyphosphates;    chelators; inorganic buffers; anions of alkylsulfates, arylsulfates,    alkylsulfonates, arylsulfonates, alkylcarboxylates,    arylcarboxylates, alkylphosphates, arylphosphates; and combinations    thereof; wherein the alkyl groups have a chain length of greater    than four carbon atoms, and the aryl groups include at least 6    carbon atoms.-   36. The oral care kit of any one of embodiments 30 through 35,    wherein the moisturizer composition has a pH of 3 to 8.-   37. The oral care kit of any one of embodiments 30 through 36,    wherein the moisturizer composition has a viscosity of at least 50    centipoise.-   38. The oral care kit of any one of embodiments 30 through 37,    wherein the multi-valent cationic antiseptic is selected from the    group consisting of biguanides, bisbiguanides, polybiguanides,    polymeric quaternary ammonium compounds, and combinations thereof.-   39. The oral care kit of embodiment 38, wherein the multi-valent    cationic antiseptic is a chlorhexidine salt.-   40. The oral care kit of any one of embodiments 30 through 39,    wherein the multi-valent cationic antiseptic composition comprises a    solution of the multi-valent cationic antiseptic at 0.05 to 0.4    weight percent.-   41. The oral care kit of any one of embodiments 30 through 40,    wherein the multi-valent cationic antiseptic is included in a    composition further comprising a sweetener selected from the group    consisting of sucralose, aspartame, xylose, sucrose, maltose,    mannose, glucose, xylitol, sorbitol, mannitol, erythritol, maltitol,    lactitol, and a combination thereof.-   42. The oral care kit of any one of embodiments 30 through 41,    wherein the kit includes at least one dose of the multi-valent    cationic antiseptic composition.-   43. The oral care kit of any one of embodiments 30 through 42,    wherein the kit includes at least 15 mL of the multi-valent cationic    antiseptic composition.-   44. The oral care kit of any one of embodiments 30 through 43,    wherein the kit includes at least 30 mL of the multi-valent cationic    antiseptic composition.-   45. The oral care kit of any one of embodiments 30 through 44,    wherein the kit includes at least two 15 mL unit dose containers of    the multi-valent cationic antiseptic composition.-   46. The oral care kit of any one of embodiments 30 through 45,    wherein the moisturizing composition is supplied in an amount    sufficient for at least one application to the oral tissue of the    subject at 1 to 10 grams per application.-   47. The oral care kit of any one of embodiments 30 through 46,    wherein the substantive moisturizing composition is supplied in an    amount sufficient for at least 4 applications to the oral tissue of    the subject at 1 to 10 grams per application.-   48. The oral care kit of embodiment 47, wherein the moisturizing    composition is supplied in at least 4 unit dose packages of 1 to 10    grams per package.-   49. The oral care kit of any one of embodiments 30 through 48,    wherein the moisturizing composition is supplied in a single    container.-   50. The oral care kit of any one of embodiments 30 through 49,    wherein the moisturizer composition has a shrinkage of less than 10    percent when dried under ambient conditions.-   51. The oral care kit of any one of embodiments 30 through 50,    wherein the substantive moisturizer composition when dried on a    surface under ambient conditions cannot be peeled from the surface    in a single piece.-   52. The oral care kit of any one of embodiments 30 through 51,    wherein the moisturizer composition when dried on a surface under    ambient conditions does not form a self supporting film.-   53. The oral care kit of any one of embodiments 30 through 52,    wherein the kit further comprises a de-briding composition.-   54. The oral care kit of embodiment 53, wherein the de-briding    composition comprises hydrogen peroxide stabilized with a component    which maintains the de-briding composition at a pH of 2.5 to 4, and    wherein the de-briding composition essentially excludes any    component which causes a precipitate when combined with a    multi-valent cationic antiseptic used in the multi-valent cationic    antiseptic composition when tested according to Test Method F.-   55. The oral care kit of embodiment 54, wherein the hydrogen    peroxide is stabilized with a buffer component selected from the    group consisting of monovalent alkyl carboxylic acids and alkyl    phosphoric acids wherein the alkyl group optionally comprises a    carbon chain substituted with or interrupted by one or more N, 0, or    S atoms; phosphate or carboxylate terminated polyethoxylated and/or    propoxylated alkyl alcohols; alpha-hydroxy acids; amino acids;    phosphoric acid; and boric acid; wherein the buffer component is    selected and used at concentrations such that a precipitate is not    formed when the buffer component is combined with the multi-valent    cationic antiseptic.-   56. The oral care kit of any one of embodiments 53, 54, and 55,    wherein the de-briding composition is supplied in an amount    sufficient for at least one application to the oral tissue of the    subject.-   57. The oral care kit of embodiment 56, wherein the de-briding    composition is supplied in at least 4 unit dose containers, each    containing an amount sufficient for a single application to the oral    tissue of the subject.-   58. The oral care kit of embodiment 57, wherein the de-briding    composition is supplied in a single container in an amount    sufficient for at least 4 applications to the oral tissue of the    subject.-   59. The oral care kit of any one of embodiments 30 through 58,    further comprising an additional oral care composition selected from    the group consisting of an oral rinse, a toothpaste, a lip care    composition, a mouth care composition, and combinations thereof.-   60. The oral care kit of any one of embodiments 30 through 59,    further comprising a plurality of applicator tools for applying at    least one composition to the oral tissue of a subject.-   61. The oral care kit of embodiment 60, wherein the plurality of    applicator tools is selected from the group consisting of swabs,    suction swabs, toothbrushes, suction toothbrushes, and combinations    thereof.-   62. The oral care kit of embodiment 60 or embodiment 61, wherein at    least a portion of the plurality of applicator tools is packaged so    that usage of the at least a portion of the plurality of applicator    tools shows compliance with at least a portion of a protocol for    treating the oral tissue of a subject.-   63. The oral care kit of embodiment 62, wherein the at least a    portion of the plurality of applicator tools is packaged with an    indication of at least one time frame for applying at least one    composition comprising the kit.-   64. The oral care kit of embodiment 63, wherein the indication is a    color code, a symbol, a picture, or a printed number.-   65. The oral care kit of any one of embodiments 60 through 64,    comprising a plurality of packages, wherein each package contains at    least one kit component selected from the group consisting of an    applicator tool, a suction yankaeur, a suction catheter, a    Y-connector, a vacuum adapter handle, a multi-valent cationic    antiseptic composition, a substantive moisturizing composition, a    de-briding composition, other mouth care products and a combination    thereof.-   66. The oral care kit of embodiment 65, wherein the package is a    bag, a box, a tray, or a combination thereof.-   67. A method of moisturizing while decolonizing mammalian tissue,    the method comprising:

applying a multi-valent cationic antiseptic composition to the tissue,and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that the multi-valent cationicantiseptic composition combined with the substantive moisturizercomposition achieves a log reduction in the number of viable bacterialcells of at least 2 when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853)are combined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B; and

wherein the anionic compound is selected from the group consisting ofpolyanions of polycarboxylates, polysulfonates, polysulfates, andpolyphosphates; chelators; inorganic buffers; anions of alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; and combinationsthereof; wherein the alkyl groups have a chain length of greater thanfour carbon atoms, and the aryl groups include at least 6 carbon atoms.

-   68. A method of moisturizing while decolonizing mammalian tissue,    the method comprising:

applying a multi-valent cationic antiseptic composition to the tissue,and

applying a substantive moisturizer composition to at least a portion ofthe same tissue;

wherein the mammalian tissue is oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that greater than 40 percent ofthe multivalent cationic antiseptic, which was soluble in themulti-valent cationic antiseptic composition, remains soluble when themulti-valent cationic antiseptic composition and the substantivemoisturizer composition are combined; and

wherein the anionic compound is selected from the group consisting ofpolyanions of polycarboxylates, polysulfonates, polysulfates, andpolyphosphates; chelators; inorganic buffers; anions of alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; and combinationsthereof; wherein the alkyl groups have a chain length of greater thanfour carbon atoms, and the aryl groups include at least 6 carbon atoms.

-   69. An oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that the multi-valent cationicantiseptic composition combined with the substantive moisturizercomposition achieves a log reduction in the number of viable bacterialcells of at least 2 when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853)are combined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B; and

wherein the anionic compound is selected from the group consisting ofpolyanions of polycarboxylates, polysulfonates, polysulfates, andpolyphosphates; chelators; inorganic buffers; anions of alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; and combinationsthereof; wherein the alkyl groups have a chain length of greater thanfour carbon atoms, and the aryl groups include at least 6 carbon atoms.

-   70. An oral care kit comprising:

a multi-valent cationic antiseptic composition comprising a multi-valentcationic antiseptic; and

a substantive moisturizing composition;

wherein each composition is for application to oral tissue of a subject;

wherein the multi-valent cationic antiseptic is other than a metal ion;and

wherein when the substantive moisturizer composition includes an anioniccompound, the anionic compound is such that greater than 40 percent ofthe multivalent cationic antiseptic which was soluble in themulti-valent cationic antiseptic composition remains soluble when themulti-valent cationic antiseptic composition and the substantivemoisturizer composition are combined; and

wherein the anionic compound is selected from the group consisting ofpolyanions of polycarboxylates, polysulfonates, polysulfates, andpolyphosphates; chelators; inorganic buffers; anions of alkylsulfates,arylsulfates, alkylsulfonates, arylsulfonates, alkylcarboxylates,arylcarboxylates, alkylphosphates, arylphosphates; and combinationsthereof; wherein the alkyl groups have a chain length of greater thanfour carbon atoms, and the aryl groups include at least 6 carbon atoms.

-   71. The method of embodiment 67 or embodiment 68 or the oral care    kit of embodiment 69 or embodiment 70, where the substantive    moisturizer composition when dry does not form a self supporting    film.-   72. A method of moisturizing oral tissue of a patient requiring    intubation, the method comprising:

applying a moisturizer composition to at least a portion of the oraltissue, an endotracheal tube, or both;

inserting an endotracheal tube through the patients oral cavity and intothe patient's trachea;

wherein the endotracheal tube is coated or impregnated with a cationicantiseptic;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the cationic antisepticwhen tested according to Test Method F; and

wherein the cationic antiseptic is other than a metal ion.

-   73. A kit comprising:

a moisturizer composition for application to oral tissue, to anendotracheal tube, or both; and

at least one endotracheal tube;

wherein the endotracheal tube is coated or impregnated with a cationicantiseptic;

wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the cationic antisepticwhen tested according to Test Method F; and

wherein the cationic antiseptic is other than a metal ion.

Objects and advantages of this invention are further illustrated by thefollowing examples, but the particular materials and amounts thereofrecited in these examples, as well as other conditions and details,should not be construed to unduly limit this invention.

EXAMPLES

TABLE 1 GLOSSARY of COMPONENTS Acronym Description Trade Name SourceLocation — Aloe Vera Gel Aloe Vera Gel Concentrated Ormond ConcentrateAloe Beach, FL Corporation — Aloe Vera Gel Aloe Terry Chicago, ILbarbadensis Laboratories leaf juice, 1x, decolorized) — BenzoicSulphimide Sodium Alfa Aesar, lot Pelham, NH Sodium Salt - 97% Saccharin# IN000161 — Carbomer 954 Carbopol 954 BFGoodrich, Cleveland, OH lot#6900029 — L-carvone — Ungerer & Co Lincoln Park, NJ CHG ChlorhexidineChlorhexidine American Framingham, Digluconate Gluconate InternationalMA 20% USP Chemical Inc. (18.6% wt/wt) — Citric Acid-Anhydrous — Sigma,lot # St. Louis, MO 023K0023 — D-Gluconic Acid Aldrich St. Louis, MO —Glycerol Glycerin USP J.T. Baker Phillipsburg, NJ — Glycerol GlycerinUSP Ecogreen Cranbury, NJ — Glyceryl — international Wayne, NJPolymethacrylate Specialty Products (ISP) HEC (hydroxyethylcellulose)Natrosol 250H Hercules Shandong China — Hydroxypropyl Guar Jaguar HP 60Rhodia Cranbury, NJ HPMC Hydroxypropylmethyl- Methocel Dow ChemicalMidland, MI cellulose K100M Company Premium — Menthol USP — SharpMenthol Delhi, India India Ltd — Methylparaben — Sharon IsraelLaboratories — Peppermint - Natural — Intarome Norwood, NJ H₃PO₄Phosphoric Acid - 85% — Aldrich Milwaukee, Chemical Co., WI lot# 11430KYKCl Potassium Chloride — J.T. Baker, Phillipsburg, lot# G28H00 NJ —Potassium Sorbate — J.T. Baker, Phillipsburg, lot# E27620 NJ —Propylparaben — Sharon Israel Laboratories C₆H₅COONa Sodium Benzoate —Alfa Aesar, Pelham, NH lot# 10102000 NaCMC Sodium — Fisher Fairlawn, NJCarboxymethyl Scientific Co., cellulose lot# 794429 NaCl Sodium ChlorideTable salt Sigma-Aldrich St. Louis, MO NaCl Sodium Chloride Table saltJ.T. Baker, Phillipsburg, lot# G32468 NJ NaOH Sodium Hydroxide —Titristar, lot# Gibbstown, 3120 NJ — Spearmint - Imitation — BelwoodRingwood, NJ Aromatics H₂O Water - Purified — 3M Laboratory St. Paul, MNDistilled Water — Xanthan Gum Keltrol TF CP Kelco San Diego, CA —Xylitol Xylitol American Framingham, NF/FCC International MA ChemicalInc. — Xylitol Xylitol Futian Melbourne, NF/FCC Pharmaceutical FL

TABLE 2 Comparative Examples of Commercially Available Oral MoisturizersComparative Example Ingredients (in order of predominance as NumberProduct Name Manf. appearing on product label) C1 Biotene LacledeHydrogenated starch hydrolysate, ORALBALANCE Inc. Glycerinpolymethacrylate, Xylitol, gel Hydroxyethyl cellulose, Beta-d-glucose,Lactoperoxidase, Lysozyme, Lactoferrin, Glucose oxidase, Potassiumthiocyanate, Aloe Vera C2 KIMVENT Kimberly- Purified Water, PropyleneGlycol, Mouth Clark Sorbitol, Hydroxypropyl Methylcellulose, MoisturizerDimethicone, Flavor, Xylitol, Aloe Vera Gel, Potassium Sorbate, SodiumBenzoate, Potassium Chloride, Sodium Chloride C3 TOOTHETTE Sage Water,Coconut Oil, Xylitol, Spearmint Mouth Products flavor, SodiumCarboxymethylcellulose, Moisturizer Inc. Vitamin E Acetate, Spearmintoil, Carbomer 974, Polysorbate 20, polysorbate 80, potassium sorbate,cetylpyridinium chloride C4 Biotene Laclede Purified Water, PropyleneGlycol, Xylitol, Mouthwash Inc. Polyglycitol, Poloxamer 407,Hydroxyethylcellulose, Sodium Benzoate, Benzoic Acid, NaturalPeppermint, Sodium Phosphate, Zinc Gluconate, Calcium Lactate, AloeVera, Potassium Thiocyanate, Natural Enzymes: Lactoferrin, Lysozyme,Lactoperoxidase, Glucose Oxidase

TABLE 3 Example Formulations of Moisturizers Example Number Example NameIngredients (% w/w) Ex 1 Example 1 Purified Water (87.8%), Xylitol (5%),Glycerol (5%), Xanthan Gum (1.6%), Hydroxypropylmethylcellulose (0.5%),Aloe Vera Gel (0.1%) Ex 2 Example 2 Purified Water (87.8%), Xylitol(5%), Glycerol (5%), Hydroxypropyl Guar (1.6%),Hydroxypropylmethylcellulose (0.5%), Aloe Vera Gel (0.1%) Ex 3 Example 3Purified Water (87.8%), Xylitol (5%), Glycerol (5%), Hydroxypropyl Guar(1.6%), Hydroxypropylmethylcellulose (0.5%), Chlorhexidine Digluconate(0.12%), Aloe Vera Gel (0.1%) Ex 4 Example 4 Purified Water (80.71%),Glycerin (15%), Hydroxypropyl Guar (1%), Hydroxyethylcellulose (1%),Xylitol (1%), Aloe Vera Gel (1%), Methylparaben (0.2%), Propylparaben(0.04%), Imitation Spearmint (0.0225%), Menthol (0.015%), NaturalPeppermint (0.01%), L-carvone (0.0025%)Test Method A—Viscosity Test

For selected Examples viscosity was measured at approximately 22° C. atambient pressure using a Brookfield viscometer, model LVT withBrookfield LV spindles. The smallest spindle and the lowest speed arealways chosen for each particular sample such that the viscometer wasoperating in the middle of its range. All samples were allowed toequilibrate at approximately 22° C. for 24 hours prior to measurement.Preferably the viscosity is taken at the lowest speed possible whilestaying within 10-90% and preferably 20-80% of the viscometer range. Inall cases the sample size and container geometry was chosen to ensurethat there were no wall effects. By “wall effects” it is meant theviscosity value is not affected by the container and is essentiallyequivalent to the viscosity taken in an infinitely large container. Forthis reason lower viscosity samples required a larger sample size toaccommodate the larger spindles. The viscosity of each sample was takenas the highest relatively stable reading that was achieved.

TABLE 4 Viscosity Results Example Viscosity Number Product Name (cps) C1ORALBALANCE Gel >2,000,000 C2 KIMVENT Mouth 80,000 Moisturizer C3TOOTHETTE Mouth 1,810,000 Moisturizer C4 Biotene Mouthwash 18 Ex 1Example 1 80,000 Ex 2 Example 2 290,000 Ex 3 Example 3 Not tested Ex 4Example 4 77,000Test Method B—Antimicrobial Efficacy Testing

This test method demonstrates the compatibility (or incompatibility) ofPERIDEX antimicrobial mouth rinse with mouth moisturizers by challengingthe mixtures with the bacteria Pseudomonas aeruginosa. If the activityof PERIDEX mixed with a moisturizer is not statistically less than theactivity of PERIDEX alone, then the moisturizer can be said to becompatible with PERIDEX. The ratio of PERIDEX:Moisturizer was chosen tomimic actual product use. When PERIDEX is applied using a swab to aventilated patient approximately 1 to 2 grams is retained in the oralcavity. Many moisturizers are supplied in 2 g unit does packets, fromwhich approximately 1 to 2 grams can be applied. In this assay, theantimicrobial activity of mixtures of PERIDEX and moisturizers is testedby inoculating 1 mL of the mixture with an inoculum of the bacteria. Atthe specified exposure time, a neutralizer for CHG and hydrogen peroxideis added, tubes are vortexed, serially diluted and plated forenumeration of surviving bacteria.

Sample Preparation for Antimicrobial Efficacy Test

Test mixtures were prepared at 2 levels (4.8 g or 6.4 g) of each of theabove moisturizers with 9 g of PERIDEX solution. PERIDEX is a solutionof 0.12% chlorhexidine gluconate (1,11-hexamethylenebis[5-(p-chlorophenyl)biguanide]di-D-gluconate) in a base containingwater, 11.6% alcohol, glycerin, PEG-40 sorbitan diisostearate, flavor,sodium saccharin, and FD&C Blue No. 1 commercially available from 3MESPE Dental Products of St. Paul, Minn. The resulting mixtures werevortexed to mix vigorously for a period of 2 minutes. The mixtures wereallowed to incubate for 15 minutes prior to centrifugation at 5000 rpmfor 30 min. The samples were centrifuged in order to settle insolublematerial. After centrifugation, supernatant was carefully transferred toa new vial and submitted for Antimicrobial Efficacy Testing, see Table 5and HPLC recovery of CHG testing, see Table 7.

Test Organism for Antimicrobial Efficacy Test

The test organism for this assay was Pseudomonas aeruginosa (ATCC27853). The initial suspension was prepared by suspending bacterialcolonies from an overnight growth plate on Tryptic Soy Agar inphosphate-buffered water (PBW). The PBW was prepared as follows: To 500ml deionized water was added 0.34 g potassium dihydrogen phosphate. ThepH was adjusted to 7.2 using 10N sodium hydroxide. The contents werediluted to 1 liter using deionized water. This was filter sterilized. A0.5 McFarland turbidity standard was used to obtain a cell density ofapproximately 1.5×10⁸ CFU/mL.

Test Materials for Antimicrobial Efficacy Test

Each moisturizer was mixed with PERIDEX in defined ratios as describedabove. PERIDEX and moisturizer were weighed into glass vials, and mixedby vortexing for a period of 2 minutes. Moisturizer samples containingCHG were not mixed with PERIDEX. Testing was conducted with 1 mL of themixtures. Duplicate 1 mL samples were transferred into 50 mL conicaltubes with a positive displacement pipet. The controls for the testingwere 1 mL of PBW (for direct enumeration of inoculum) and 1 mL PERIDEX.

Inoculum Preparation for Antimicrobial Efficacy Test

The inoculum was prepared by diluting the initial suspension 10 fold inPBW. The inoculum suspension was enumerated at the beginning and end ofthe test period. The final count was within 0.1 log/mL of the initialcount. Each 1 mL test sample was inoculated with approximately 5.8 logsbacteria.

Neutralizing Broth: The D/E broth is Dey Engley neutralizing brothpurchased as a solid and reconstituted according to directions fromDifco Laboratories, Detroit Mich. The D/E broth was supplemented withfilter-sterilized Catalase (from bovine liver, Calbiochem, 0.2 g/literbroth) immediately before use.

Test Method B—Measurement of Antimicrobial Activity:

Forty microliters of the bacterial inoculum was added to one mL of thetest mixtures, vortexed and let sit at ambient temperature. Timingstarted as soon as the bacteria were added. After 2.5 minutes, 20 mL ofD/E broth containing catalase was added and vortexed vigorously.

Dilutions were prepared in PBW, and 1 mL, in duplicate, pipetted intoAerobic Count Petrifilm Plates, 3M Company. All plates were incubated at35° C. for 43 hours. Plates were counted with the 3M Petrifilm PlateReader, and confirmed manually. Colony Forming Units (CFU) were counted,duplicate plates averaged and multiplied by the dilution factor forCFU/mL, and multiplied by the total test volume after neutralization (21mL) for the CFU/test sample. Log 10 CFU/test of duplicate tests wereaveraged and the log 10 reduction was calculated from the PBW controls.

The mixtures of PERIDEX with the comparative examples C1, C2, C3 andexperimental examples Ex 1, Ex 2 and Ex 3 were tested according to theabove Antimicrobial Efficacy Test. The results are shown in Table 5,below. Mixtures of PERIDEX with KIMVENT Mouth Moisturizer, 3M XanthanGel and 3M Guar Gel did not significantly impact the antimicrobialefficacy of CHG. All performed equivalent to PERIDEX oral rinse testedunder the same conditions. 3M Guar Gel with 0.12% CHG also performedsimilarly to the PERIDEX control. In contrast, mixtures of PERIDEX withORALBALANCE Gel and TOOTHETTE Mouth moisturizer significantly decreasedthe antimicrobial efficacy of CHG. Both ORALBALANCE Gel and TOOTHETTEmoisturizers achieved less than 2 log reduction of bacteria.

TABLE 5 RESULTS FOR TEST METHOD B - ANTIMICROBIAL EFFICACY TESTMoisturizer Example Grams of Grams of Log Number PERIDEX MoisturizerReduction C1 1.5 0.8 1.5 C1 1.5 1.1 1.5 C3 1.5 0.8 0.5 C3 1.5 1.1 0.6 Ex1 1.5 0.8 4.6 Ex 1 1.5 1.1 5.0 Ex 2 1.5 0.8 5.4 Ex 2 1.5 1.1 5.7 Ex 3 01.1 4.3 Control* 1.5 0 5.7 *Control = PERIDEX only

The TOOTHETTE mouth moisturizer C3 was tested in increasing ratios ofmoisturizer:PERIDEX according to the Antimicrobial Efficacy Test,described above. The results are shown in Table 6, below. Virtuallycomplete kill of bacteria is achieved with PERIDEX when it isuninhibited by moisturizer C3. However, as little as 0.2 grams ofTOOTHETTE moisturizer impacts the antimicrobial efficacy of PERIDEX.With increasing levels of moisturizer C3, the log reduction is furtherreduced.

Additional test mixtures were prepared across a range of levels (1.2 g,2.4 g, 4.8 g, 6.0 g, and 6.4 g) of commercially available C3 moisturizer(TOOTHETTE Mouth Moisturizer), each weighed into a vial containing 9 gof PERIDEX solution. The resulting mixtures were vortexed for a periodof 2 minutes. The mixtures were allowed to incubate for 15 minutes priorto centrifugation at 5000 rpm for 30 min. After centrifugation,supernatant was carefully transferred to a new vial and submitted forAntimicrobial Efficacy Testing, see Table 6 and HPLC recovery of CHGtesting, see Table 8.

TABLE 6 ANTIMICROBIAL EFFICACY TEST RESULTS Increasing Amounts of C3Moisturizer Grams of C3 Grams of Average Log Moisturizer PERIDEXReduction 0.2 1.5 1.9 0.4 1.5 1.3 0.8 1.5 0.5 1.0 1.5 0.6 1.1 1.5 0.6Control 0.0 1.5 5.7Test Method C—Percent Recovery of CHG by HPLC Analysis

HPLC analysis was performed to approximate the amount of available CHG,not “inhibited” by the moisturizer. Reverse phase gradient HPLC analysisof the provided solutions/suspensions were performed using an Agilent1200 SLMSD system consisting of a binary SL pump, well plateautosampler, heated column compartment and diode array absorbancedetector (DAD). Separations were performed under the followingchromatographic conditions. The sample injection volume was 10 μL. TheHPLC column used was a 4.6×75 mm, Zorbax 3.5 μm SB-C18 column (Agilent).Column temperature was maintained at 35° C. The flow rate was 0.5mL/min. The mobile phase consisted of 2 solvent mixtures: solvent A=100%water+0.1% v/v TFA and Solvent B=100% Methanol+0.1% v/v TFA. Aprogrammed linear gradient mobile phase was used: 90/10 SolventA/Solvent B (0 minute hold) to 100% B (5 minute hold) over eight minutes(linear). Step back to initial conditions, 5 minute re-equilibration.Elution time for chlorhexidine was approximately 13.1 minutes. Detectionwas by UV-VIS at 258 nm (reference=450 nm). A linear regressioncalibration curve of the equivalent chlorhexidine response was performedusing volumetric standard solutions at 4 levels of chlorhexidine freebase. The standards were run both before and after the sampleinjections. Absorbance data was averaged from duplicate injections fromeach sample, as well as duplicate samples and concentrations determinedbased on standards. The equivalent concentrations of CHG were calculatedbased on the 1.78 fold difference in molecular weights. The CHGcontrol-PERIDEX control is calculated to be 0.133 wt % from HPLC.

Prior to analysis by HPLC samples were prepared in the following manner.Quantitatively, 50-150 mg of each of the above test mixtures weretransferred to a vial. An amount of 5 mL of extraction solvent (90/10water/methanol+0.1% v/v TFA) was added to the test mixtures. All sampleswere vortexed briefly and allowed to extract/dissolve for a period of 4hours at room temperature on an orbital shaker. After extraction for 4hours, samples were transferred to HPLC vials. Samples were ready forHPLC analyses.

TABLE 7 HPLC % Recovery of CHG in the Presence of Different Types ofMoisturizers Grams of Grams of % Recovery of Moisturizer PERIDEXMoisturizer CHG C1 (ORALBALANCE) 1.5 1.1 33.3% C2 (KIMVENT) 1.5 1.1104.4% C3 (TOOTHETTE) 1.5 1.1 26.7% Ex 1 (Xanthan gel) 1.5 1.1 97.8% Ex2 (Guar gel) 1.5 1.1 106.7% Ex 3 (Guar gel + CHG) 1.5 1.1 100.0% Control(PERIDEX only) 1.5 0 100.0% Percent Recovery of soluble CHG was comparedto control using 90% water/10% methanol/0.1% TFA for solubilization ofCHG

TABLE 8 HPLC % Recovery of CHG in the Presence of Different Levels ofMoisturizer Grams of C3 Grams of % Recovery Moisturizer PERIDEX of CHG0.2 1.5 40.3% 0.4 1.5 25.0% 0.8 1.5 18.2% 1.0 1.5 13.2% Control 0.0 1.5100.0% % Recovery of soluble CHG was compared to control using 90%water/10% methanol/0.1% TFA for solubilization of CHG

Still more test mixtures were prepared with different amounts ofpotentially inhibitory reagents including: Carbopol and NaCl, eachweighed into a vial containing an equal amount of PERIDEX solution,resulting in 1:1 mixtures as shown in Table 9. The resulting mixtureswere vortexed for a period of 2 minutes. The mixtures were allowed tostand at ambient conditions for 15 minutes prior to centrifugation at5000 rpm for 30 min. After centrifugation, supernatant was carefullytransferred to a new vial and submitted for Test Method C, HPLC recoveryof CHG testing, see Table 9.

TABLE 9 HPLC % Recovery of CHG in the Presence of Inhibitory Reagents %Recovery Description of Samples of CHG 1:1 soln of 1% Carbopol954:PERIDEX 17.91% 1:1 soln of 10% Carbopol 954:PERIDEX 17.91% 1:1 solnof 1% NaCl:PERIDEX 38.91% 1:1 soln of 10% NaCl:PERIDEX 28.36% Control(PERIDEX only) 100.00% % Recovery of soluble CHG was compared to controlusing 90% water/10% methanol/0.1% TFA for solubilization of CHGTest Method D—Moisturizer Film Formation and Caking

An amount of 0.2 grams of a moisturizer was weighed onto the center of a2.5×2.5 cm (1×1 inch) square marked on a clear plastic petri dish, 15 mmpolystyrene plastic disposable sterile dish (Cat #25384-088, VWR WestChester, Pa.). The 0.2 grams of moisturizer was spread evenly tocompletely coat the 2.5×2.5 cm (1×1 inch) area of a clear plastic petridish. Films were left to dry at room temperature in open air conditionsfor 2 hours. After 2 hours, visual and physical observations were madefor each dried film. The fraction of area still covered by the driedfilm was visually observed. Films were physically characterized bypeeling the film off of the plastic dish and observing the amount peeledoff of the petri dish as a single piece, and the ease with which thefilm can be torn or broken when pulled. Results are shown in Table 10,below.

TABLE 10 Moisturizer Film Formation Results Moisturizer Film ContractionFilm Peeling C2 The film shrank The entire film was removed as asignificantly. Only single piece. It was a self- ⅓ of the 2.5 cmsupporting film. The piece was square area was elastic and could not beeasily covered broken or torn. Ex 1 The entire No significant portion ofthe film 2.5 cm square was able to be peeled off of the petri arearemained dish. A self-supporting film could coated not be recovered. Ex2 The entire Approximately ¼ of the coated area 2.5 cm square was peeledoff as a single piece area remained before breaking. The film was verycoated thin, non-elastic and easily torn. The portion that could beremoved formed a self-supporting film.Test Method E—Demonstration of SubstativityGeneral Description of Substantivity Test Method:

A substantive moisturizer composition was defined by the ease with whichdyed moisturizer sample was washed away from an artificial skin surface,VITRO-SKIN available from IMS Inc. of Portland, Md.). Moisturizersamples included competitive sample C4, Example Ex4, dilutions of Ex4 indistilled water (represented as wt % Ex4), and distilled water alone asa control.

Viscosity Measurement of Moisturizer Samples:

The viscosity of each moisturizer sample or diluted moisturizer samplewas measured using a Brookfield viscometer; model LVT with Brookfield LVspindles, as described in the viscosity test. The viscosity of eachsample is shown with the results in Table 11.

Dying of Moisturizer Samples for Substantivity Testing:

After measurement of viscosity, each sample was dyed to make themoisturizer sample easily visible in water. The dye was selected toensure that it does not stain VITRO-SKIN. For the current example,moisturizers were dyed by adding 0.3 grams of BETADINE (10% PovidoneIodine, available from Purdue Products L.P. of Stamford, Conn.) to 5grams of moisturizer or diluted moisturizer sample. The staining ofVITRO-SKIN was verified by placing a drop of BETADINE on the topographyside of VITRO-SKIN (prepared as described below), waiting for 1 minute,washing it off in distilled water, and visually confirming the absenceof color. For moisturizer samples that are incompatible with povidoneiodine, another dye could be used that, similarly, does not stainVITRO-SKIN.

Preparation of VITRO-SKIN for Substantivity Testing:

VITRO-SKIN was pre-hydrated in a chamber at 75° F. (24° C.) and 45%relative humidity (RH). The pre-hydrated VITRO-SKIN was cut into 2.5×2.5cm (1×1 inch) squares and a black permanent ink marker was used to markthe edges of VITRO-SKIN to make it more visible for manipulation. Thesquares of VITRO-SKIN were dunked in distilled water for 5 seconds tosimulate a moist tissue surface, and placed at the bottom of a dry 8 oz.glass jar, with the topography (non-shiny) side facing up.

Substantivity Test Method:

Each dyed sample (0.5 grams) was pipetted onto the surface of theprepared VITRO-SKIN square in the bottom of its 8 oz. glass jar.Observations were made regarding the surface interaction between thesample and the VITRO-SKIN. Distilled water (25 mL) was added to the jarby pipetting the water down the side of the jar, carefully, to ensurethat the contact between the sample and the VITRO-SKIN was not disturbedby the flow of water. After 1 minute (starting at the time water beginsto enter the jar), the VITRO-SKIN and any contacting, dyed sample wascarefully removed from the jar using tweezers, placed on a clean, drypaper towel, and photographed. The sample was carefully returned to thejar and re-submerged in the water, where it was allowed sit forapproximately 1 hour and 30 minutes. After 1 hour and 30 minutes, theVITRO-SKIN and any contacting, dyed sample was, again, carefully removedfrom the jar using tweezers, placed on a clean, dry paper towel, andphotographed. The photographed images were visually characterizedaccording to the amount of surface area covered by the dyed sample, theintensity of the dyed sample, and the relative thickness of the film orpool of dyed sample remaining on the VITRO-SKIN. The results forsubstantivity of the tested moisturizers are summarized in Table 11 withreported observations made initially, after 1 minute and after 1.5hours.

TABLE 11 DEMONSTRATION OF SUBSTANTIVITY Observations Initially Viscosityafter sample pipetted onto Observations Observations Sample (cps)VITRO-SKIN after 1 minute after 1.5 hours C4 18 Sample flows over the Nosample No sample entire surface of the remaining on the remaining onVITRO-SKIN and runs off VITRO-SKIN the VITRO- of the edge onto thebottom Not Substantive SKIN of the jar Not Substantive Water 0 Sampledoes not wet the No sample No sample VITRO-SKIN well and remaining onthe remaining on runs off the edge onto the VITRO-SKIN the VITRO- bottomof the jar Not Substantive SKIN Not Substantive 10% 11.3 Sample does notNo sample No sample Ex4 completely wet VITRO- remaining on the remainingon SKIN and the majority runs VITRO-SKIN the VITRO- off the edge ontothe Not Substantive SKIN bottom of the jar. The Not Substantive amountof sample remaining on (wetting) the VITRO-SKIN is more than observedfor the Water sample. 15% 16.6 Sample does not No sample No sample Ex4completely wet VITRO- remaining on the remaining on SKIN and themajority runs VITRO-SKIN the VITRO- off the edge onto the NotSubstantive SKIN bottom of the jar. The Not Substantive amount of sampleremaining on (wetting) the VITRO-SKIN is more than observed for the 10%Ex4 sample. 25% 113 Sample wets VITRO-SKIN A thin layer of No sample Ex4and the majority remains in light brown to remaining on contact withVITRO-SKIN. yellow sample the VITRO- Some runs off the edge over half ofthe SKIN onto the bottom of the jar. area of the Not Substantive Theamount of sample VITRO-SKIN is remaining on (wetting) the observed.VITRO-SKIN is more than Substantive observed for the 15% Ex4 sample. 33%300 Sample wets VITRO-SKIN A dark brown/red No sample Ex4 and themajority remains in layer is observed remaining on contact withVITRO-SKIN. over 90% of the the VITRO- Some runs off the edgeVITRO-SKIN. SKIN onto the bottom of the jar. Substantive Not SubstantiveThe amount of sample remaining on (wetting) the VITRO-SKIN is more thanobserved for the 25% Ex4 sample 50% 1,734 Sample forms a large pool Adark brown/red No sample Ex4 on VITRO-SKIN and layer, thicker thanremaining on nearly the entire sample that observed for the VITRO-remains in contact with the 33% Ex4 SKIN VITRO-SKIN. Very little sample,covers Not Substantive runs off the edge onto the 80% of the bottom ofthe jar. The VITRO-SKIN. It amount of sample appears that the remainingon (wetting) the original pool is VITRO-SKIN is more than still intact.observed for the 33% Ex4 Substantive sample Ex4 77,000 Sample forms alarge pool A dark brown/red A thin on VITRO-SKIN and the layer, thickerthan red/brown layer entire sample remains in that observed for covering~75% contact with VITRO-SKIN. the 50% Ex4 VITRO-SKIN is None runs offthe edge onto sample, covers observed. It the bottom of the jar. The 80%of the appears to be in entire square is not coated VITRO-SKIN. It thesame because the moisturizer appears that the location/area as sample ispooled in the original pool is the original pool center. still intact.of sample. Substantive SubstantiveTest Method—Evaluation Precipitate Formation

It is thought that some excipients (inactives) may form a CHG complex,which is visible as a precipitate. Thus, CHG which complexes with anexcipient, forming a precipitate would not be available forantimicrobial efficacy. The purpose of the precipitation formationtesting was to observe the potential of an excipient to form aprecipitates with CHG under the following test conditions.

A solution containing 3.72% (w/w) CHG was prepared by diluting 18.6% w/wCHG stock solution with water. Sample excipient solutions were preparedwith distilled water to various concentrations of excipients accordingto Tables 12-16, below. The pH of the solutions was then adjusted toboth a low pH and a high pH using either gluconic acid or NaOH. Then 6mL of each pH adjusted excipient sample solution was transferred into aseparate vial and an equal amount (6 mL) of 3.72% CHG was added to forma 1:1 mixture (12 mL total). After combining the CHG solution with theexcipient solution, the vial of the mixture was briefly swirled to mix.The mixtures were visually assessed for the presence/formation of aprecipitate within 30 minutes. The results are shown in Tables P1-P5,where “Y” means precipitate was observed; “N” means no precipitate wasobserved; “*1” means the mixture could not be tested because a gel-likemass was formed when adding gluconic acid to reduce the pH down; and“*2” means the mixture could not be tested because it started to thickenwhen adding NaOH to raise the pH. For all the samples evaluated forformation of precipitate the weight percent of CHG was 3.72%, thisequated to 0.22 grams CHG. Since CHG has a molecular weight of 897.8;each sample had 0.245 mMol CHG, which is 0.123 milliequivalents of CHG.

TABLE 12 P1 P2 P3 P4 P5 P6 Inactive Sodium Sodium Sodium PotassiumPotassium Potassium Saccharin Saccharin Saccharin Sorbate SorbateSorbate Inactive wt % 2.00 1.00 0.50 2.00 1.00 0.50 Inactive (grams)0.12 0.06 0.03 0.12 0.06 0.03 Low pH 3.98 4.00 3.95 5.40 5.09 4.65Precipitation at Y Y Y *1 *1 *1 Low pH High pH 6.94 6.90 7.05 6.91 6.716.95 Precipitation at Y Y Y Y Y Y High pH

TABLE 13 P7 P8 P9 P10 P11 P12 Inactive Sodium Sodium Sodium KCL KCL KCLBenzoate Benzoate Benzoate Inactive wt % 2.00 1.00 0.50 2.00 1.00 0.50Inactive 0.12 0.06 0.03 0.12 0.06 0.03 (grams) Low pH 5.22 4.74 4.503.84 3.80 4.12 Precipitation at Y Y Y Y Y N Low pH High pH 7.07 7.117.18 7.10 7.21 7.09 Precipitation at Y Y Y Y Y N High pH

TABLE 14 P13 P14 P15 P16 P17 P18 Inactive NaCl NaCl NaCl H₃PO₄ H₃PO₄H₃PO₄ Inactive wt % 2.00 1.00 0.50 2.00 1.00 0.50 Inactive (grams) 0.120.06 0.03 0.12 0.06 0.03 Low pH 4.04 3.90 4.13 4.25 4.12 4.21Precipitation at Y Y Y Y Y Y Low pH High pH 6.94 6.90 6.95 6.92 6.956.76 Precipitation at Y Y Y Y Y Y High pH

TABLE 15 P19 P20 P21 P22 P23 P24 Inactive Citric Citric Citric NaCMCNaCMC NaCMC Acid Acid Acid (cellulose (cellulose (cellulose gum) gum)gum) Inactive wt % 2.00 1.00 0.50 2.00 1.00 0.50 Inactive 0.12 0.06 0.030.12 0.06 0.03 (grams) Low pH 4.00 4.18 3.98 4.31 4.24 4.23Precipitation at Y Y Y Y Y Y Low pH High pH 6.95 6.96 7.04 7.04 6.967.36 Precipitation at Y Y Y Y Y Y High pH

TABLE 16 P25 P26 P27 P28 P29 P30 Inactive Carbomer Carbomer CarbomerGlyceryl Glyceryl Glyceryl 954 954 954 Polymeth Polymeth Polymethacrylate acrylate acrylate Inactive wt % 2.00 1.00 0.50 2.00 1.00 0.50Inactive (grams) 0.12 0.06 0.03 0.12 0.06 0.03 Low pH *2 *2 3.82 3.934.04 3.94 Precipitation at *2 *2 Y Y Y Y Low pH High pH *2 *2 *2 7.287.07 7.16 Precipitation at *2 *2 *2 Y Y Y High pH

TABLE 17 P31 P32 P33 P34 P35 Inactive Hydroxypropyl HEC Aloe XanthanHPMC Guar Natrosol Vera gum Jaguar HP-60 250H gel Inactive wt % 1.0 1.0 1.0  1.6  0.5  Low pH 3.7 4.08 3.96 4.47 3.93 Precipitation at N N N N NLow pH High pH 7.9 6.75 7.02 7.27 7.23 Precipitation at N N N N N HighpHSample Preparation for:Test Method B2—Second Antimicrobial Efficacy TestingTest Method C2—Second % Recovery of CHG by HPLC Analysis

Additional samples were prepared to be assayed by HPLC and byAntimicrobial Efficacy. These additional samples were selected torepresent some of the excipients which also caused precipitation,according to the results shown in Tables 12-16. The excipients(inactives) chosen for this experiment included Carbomer, NaCMC, sodiumsaccharin, glyceryl polymethacrylate. These excipients (inactives) wereprepared as 0.5% wt/wt solutions and were adjusted to the pH valuesindicated in the table below. A 0.22% wt/wt solution of CHG was preparedat a pH of 6. All pH adjustments were made using either gluconic acid orsodium hydroxide. Each of the above excipient solutions (5 mL) weremixed with an equal amount (5 mL) of CHG solution (0.22% wt/wt). Themixtures were allowed to stand for 15 minutes at ambient conditions,along with a control CHG solution. All of these samples were centrifugedat 14,000 g for 15 minutes. After centrifugation, supernatant wascarefully transferred to a new vial and submitted for AntimicrobialEfficacy testing (TEST METHOD B2) and HPLC testing (TEST METHOD C2), seebelow.

Test Method B2—Second Antimicrobial Efficacy Testing

For Test Method B2 the above Test Method B was followed, with thefollowing changes:

-   -   1. Bacteria was MRSA (methicillin-resistant Staphylococcus        aureus), ATCC 33592, instead of P. aeruginosa.    -   2. Inoculum level was approximately 6.2 logs, instead of 5.8        logs.    -   3. Incubation time with MRSA was 4 minutes, instead of 2.5        minutes.    -   4. Neutralizer was Neutralizing Buffer, instead of D/E        Neutralizing Broth.    -   5. Incubation of the Petrifilm plates was 38 hours, instead of        43 hours.        HPLC Test Method C2—Second % Recovery of CHG by HPLC Analysis

HPLC analysis was performed to approximate the amount of available CHG,not “inhibited” by the moisturizer. Reverse phase gradient HPLC analysisof the provided solutions/suspensions were performed using an Agilent1100 system consisting of a binary pump, 100-position autosampler,heated column compartment and diode array absorbance detector (DAD).Separations were performed under the following chromatographicconditions. The sample injection volume was 0.5 uL. The HPLC column usedwas an Agilent Zorbax 4.6×75 mm, 3.5 μm SB-C18 column. The columntemperature was maintained at 40° C. The flow rate was 0.5 mL/min. Themobile phase consisted of 2 solvent mixtures: solvent A=100% water+0.1%v/v TFA and Solvent B=100% Methanol+0.1% v/v TFA. A programmed lineargradient mobile phase was used: 70/30 Solvent A/Solvent B (2 minutehold) to 100% B (2 minute hold) over 15 minutes (linear). Step back toinitial conditions, 5 minute re-equilibration. Elution time forchlorhexidine was approximately 12.7 minutes. Detection was by UV-VIS at260 nm (reference=550 nm). A percent recovery value was calculated foreach inhibitory agent (IA) by ratioing the integrated peak area for theIA with the integrated peak area for the control sample*100 (i.e.[(Integrated peak area IA/Integrated peak area control)*100]). Thepercent recovery of CHG results are reported in table 18, below.

TABLE 18 Excipient Log HPLC (Inactive) CHG Reduction % Recovery Samplewt % wt % pH of MRSA CHG CHG Control 0.0 0.22 — 3.0 100.0 Carbomer 9540.50 0.22 5.82 0.0 15.6 Glyceryl 0.50 0.22 5.89 1.9 90.2Polymethacrylate NaCMC (cellulose 0.50 0.22 6.04 0.5 38.0 gum) SodiumSaccharin 0.50 0.22 6.04 0.0 0.1Additional ANTIMICROBIAL EFFICACY testing was done on Example 4according to the following test method.Test Method B3—Antimicrobial Efficacy TestingTest Organism for Antimicrobial Efficacy Test Method B3

The test organism for this assay was Pseudomonas aeruginosa (ATCC27853). The initial suspension was prepared by suspending bacterialcolonies from overnight growth on Sheep Blood Agar in 0.3 mMphosphate-buffered water (PBW). The stock PBW (0.25M) was prepared asfollows: To 500 ml deionized water was added 34 g potassium dihydrogenphosphate. The pH was adjusted to 7.2 using 10N sodium hydroxide. Thecontents were diluted to 1 liter using deionized water. This was filtersterilized. Then 0.62 microLiters of stock solution were added to 500 mLDI water making a 0.3 mM PBW solution. A 0.5 McFarland turbiditystandard was used to obtain a cell density of approximately 1.5×10⁸CFU/mL. The suspension was enumerated at the beginning of the testperiod.

Inoculum Preparation for Antimicrobial Efficacy Test B3

The inoculum was prepared by diluting the initial suspension 10-fold inPBW. Each test sample was inoculated with approximately 5.5 logsbacteria.

Neutralizing Broth: D/E Neutralizing Broth was purchased as a solid andreconstituted according to directions from Difco Laboratories, DetroitMich.

Test Materials for Antimicrobial Efficacy Test B3

The test mixture was prepared at a ratio of 1 mL PERIDEX plus 1 gmoisturizer Example 4, plus 0.5 mL phosphate buffered water (PBW) andmixed by vortexing. The mixture was incubated at ambient temperature for5 minutes prior to inoculation. The controls for the testing were 1 mLof PBW (for direct enumeration of inoculum) and 1 mL PERIDEX.

Test Method B3—Measurement of Antimicrobial Activity:

The mixture and controls were inoculated with forty microliters ofbacterial inoculum per mL, and vortexed for 20 seconds. After 5 minutesat ambient temperature, 1 mL of the inoculated test mixture or controlswere added to 20 mL D/E Neutralizing Broth and vortexed.

Dilutions were prepared in PBW, and 1 mL, in duplicate, was pipettedinto Aerobic Count Petrifilm Plates, 3M Company. All plates wereincubated at 37° C. for 48 hours.

Plates were counted with the 3M Petrifilm Plate Reader, and confirmedmanually.

Colony Forming Units (CFU) were recorded, duplicate plates averaged andmultiplied by the dilution factor for CFU/mL, and multiplied by thetotal test volume after neutralization (21 mL) for the CFU/test sample.Log 10 CFU/test of multiple tests were averaged and the log 10 reductionwas calculated from the mean PBW control. The log 10 reduction ofPseudomonas for the test mixture of 1:1:0.5 (Peridex:3M moisturizer:PBW)was 4.4 log units. The log 10 reduction of Pseudomonas for the Controlmixture of 1:1:0.5 (Peridex:PBW:PBW) was 4.5 log units.

The complete disclosures of the patents, patent documents, andpublications cited herein are incorporated by reference in theirentirety as if each were individually incorporated. Variousmodifications and alterations to this invention will become apparent tothose skilled in the art without departing from the scope and spirit ofthis invention. It should be understood that this invention is notintended to be unduly limited by the illustrative embodiments andexamples set forth herein and that such examples and embodiments arepresented by way of example only with the scope of the inventionintended to be limited only by the claims set forth herein as follows.

What is claimed is:
 1. A method of moisturizing while decolonizingmammalian tissue, the method comprising: applying a multi-valentcationic antiseptic composition to oral tissue, wherein the multivalentcationic antiseptic persists on oral tissue for up to 5 hours, andapplying a moisturizer composition to at least a portion of the oraltissue; wherein the moisturizer composition is applied 4 hours or lessbefore or 4 hours or less after applying the multi-valent cationicantiseptic composition; wherein the moisturizer composition essentiallyexcludes any component which causes a precipitate when combined with amulti-valent cationic antiseptic used in the multi-valent cationicantiseptic composition when tested according to Test Method F; whereinthe multi-valent cationic antiseptic is other than a metal ion; andwherein the essentially excluded component is selected from the groupconsisting of polyanions of polycarboxylates, polysulfonates,polysulfates, and organic and inorganic polyphosphates; anions ofalkylsulfates, arylsulfates, alkylsulfonates, arylsulfonates,alkylcarboxylates, arylcarboxylates, alkylphosphates, arylphosphates;halide salts; and combinations thereof, wherein the alkyl groups have achain length of greater than 6 carbon atoms and the aryl groups have 6or more carbon atoms, and wherein the essentially excluded component isnot present or present at a concentration less than 0.1 percent byweight of the composition, except halide salts which are not present orpresent at a concentration not greater than 0.2 wt-% by weight of thecomposition.
 2. The method of claim 1, wherein the moisturizercomposition is such that a log reduction in the number of viablebacterial cells of at least 2 is provided when 10⁶ cfu of Pseudomonasaeruginosa (ATCC 27853) are combined with a mixture of 1.1 g of themoisturizer composition and 1.5 g of a multi-valent cationic antisepticcomposition containing 0.12 weight percent of the multi-valent cationicantiseptic according to Test Method B.
 3. A method of moisturizing whiledecolonizing mammalian tissue, the method comprising: applying amulti-valent cationic antiseptic to the tissue wherein the multivalentcationic antiseptic persists on the tissue for up to 5 hours, andapplying a substantive moisturizer composition to at least a portion ofthe same tissue; wherein the moisturizer composition is applied 4 hoursor less before or 4 hours or less after applying the multi-valentcationic antiseptic; wherein the mammalian tissue is oral tissue of asubject; wherein the multi-valent cationic antiseptic is other than ametal ion; wherein the substantive moisturizer composition is such thata log reduction in the number of viable bacterial cells of at least 2 isprovided when 10⁶ cfu of Pseudomonas aeruginosa (ATCC 27853) arecombined with a mixture of 1.1 g of the substantive moisturizercomposition and 1.5 g of a multi-valent cationic antiseptic compositioncontaining 0.12 weight percent of the multi-valent cationic antisepticaccording to Test Method B; and wherein the substantive moisturizercomposition essentially excludes a component selected from the groupconsisting of polyanions of polycarboxylates, polysulfonates,polysulfates, and polyphosphates; chelators; inorganic buffers; anionsof alkylsulfates, arylsulfates, alkylsulfonates, arylsulfonates,alkylcarboxylates, arylcarboxylates, alkylphosphates, arylphosphates;and combinations thereof; wherein the alkyl groups have a chain lengthof greater than four carbon atoms, and the aryl groups include at least6 carbon atoms.
 4. The method of claim 1, wherein the moisturizercomposition has a pH of 3 to
 8. 5. The method of claim 1, wherein themoisturizer composition has a viscosity of at least 50 centipoise. 6.The method of claim 1, wherein the multi-valent cationic antiseptic isselected from the group consisting of biguanides, bisbiguanides,polybiguanides, polymeric quaternary ammonium compounds, andcombinations thereof.
 7. The method of claim 6, wherein the multi-valentcationic antiseptic is a chlorhexidine salt.
 8. The method of claim 1,wherein the multi-valent cationic antiseptic is included in acomposition further comprising a sweetener selected from the groupconsisting of sucralose, aspartame, xylose, sucrose, maltose, mannose,glucose, xylitol, sorbitol, mannitol, erythritol, maltitol, lactitol,and a combination thereof.
 9. The method of claim 1, wherein themoisturizer composition has a shrinkage of less than 10 percent whendried under ambient conditions for 2 hours and/or wherein themoisturizer composition when dried on a surface under ambient conditionsdoes not form a self supporting film.
 10. The method of claim 1, furthercomprising applying a de-briding composition comprising hydrogenperoxide.
 11. The method of claim 10, wherein the hydrogen peroxide isstabilized with a component which maintains the de-briding compositionat a pH of 2.5 to 4, and wherein the de-briding composition essentiallyexcludes any component which causes a precipitate when combined with amulti-valent cationic antiseptic used in the multi-valent cationicantiseptic composition when tested according to Test Method F.
 12. Amethod of moisturizing oral tissue of a patient requiring intubation,the method comprising: applying a moisturizer composition to at least aportion of the oral-tissue, an endotracheal tube, or both; inserting anendotracheal tube through the patients oral cavity and into thepatient's trachea; wherein the endotracheal tube is coated orimpregnated with a cationic antiseptic; wherein the moisturizercomposition is applied 4 hours or less after inserting said tube;wherein the moisturizer composition essentially excludes any componentwhich causes a precipitate when combined with the cationic antisepticwhen tested according to Test Method F; wherein the essentially excludedcomponent is selected from the group consisting of polyanions ofpolycarbox, lapolysulfonates, polysulfates, and organic and inorganicpolyphosphates; anions of alkylsulfates, arylsulfates, alkylsulfonates,arylsulfonates, alkylcarboxylates, arylcarboxylates, alkylphosphates,arylphosphates; halide salts; and combinations thereof, wherein thealkyl groups have a chain length of greater than 6 carbon atoms and thearyl groups have 6 or more carbon atoms, and wherein the essentiallyexcluded component is not present or present at a concentration lessthan 0.1 percent by weight of the composition, except halide salts whichare not present or present at a concentration not greater than 0.2 wt-%by weight of the composition; and wherein the cationic antiseptic isother than a metal ion.
 13. The method of claim 1, wherein themoisturizer composition is applied in at least one additionalapplication.
 14. The method of claim 3, wherein the substantivemoisturizer composition is applied in at least one additionalapplication.
 15. The method of claim 12, wherein the substantivemoisturizer composition is applied to the oral tissue in at least oneadditional application.
 16. The method of claim 1, wherein theessentially excluded component is further selected from the groupconsisting of sodium saccharin, potassium sorbate, sodium benzoate,potassium chloride, sodium chloride, phosphoric acid, citric acid,sodium carboxymethylcellulose, carbomers, and glyceryl polymethacrylate.17. The method of claim 3, wherein the essentially excluded component isfurther selected from the group consisting of sodium saccharin,potassium sorbate, sodium benzoate, potassium chloride, sodium chloride,phosphoric acid, citric acid, sodium carboxymethylcellulose, carbomers,and glyceryl polymethacrylate.
 18. The method of claim 12, wherein theessentially excluded component is further selected from the groupconsisting of sodium saccharin, potassium sorbate, sodium benzoate,potassium chloride, sodium chloride, phosphoric acid, citric acid,sodium carboxymethylcellulose, carbomers, and glyceryl polymethacrylate.